User:Marcin Jozef Suskiewicz/Sandbox MarcinSuskiewicz - Revision history

Marcin Jozef Suskiewicz at 07:06, 17 November 2010

Marcin Jozef Suskiewicz — Wed, 17 Nov 2010 07:06:17 GMT

←Older revision		Revision as of 07:06, 17 November 2010
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-	NodS is a bacterial methyltransferase involved in the pathway leading to the biosynthesis of Nod factor, an important signaling molecule released by rhizobial bacteria in the course of endosymbiotic interaction with legumes. It is the first S-adenosyl-L-methionine-dependent methyltransferase specific for chitooligosaccharide substrates, the structure of which has been solved, with ([[3ofk]]) and without ([[3ofj]]) S-adenosyl-L-homocysteine ligand, which is chemically very similar to the methyl donor used by NodS, S-adenosyl-L-methionine.<ref>PMID:19052372</ref><ref>PMID: 20970431</ref>	+	NodS is a bacterial methyltransferase involved in the pathway leading to the biosynthesis of Nod factor, an important signaling molecule released by rhizobial bacteria in the course of endosymbiotic interaction with legumes. NodS from ''Bradyrhizobium japonicum'' WM9 is the first S-adenosyl-L-methionine-dependent methyltransferase specific for chitooligosaccharide substrates, the structure of which has been solved, with ([[3ofk]]) and without ([[3ofj]]) S-adenosyl-L-homocysteine ligand, which is chemically very similar to the methyl donor used by NodS, S-adenosyl-L-methionine.<ref>PMID:19052372</ref><ref>PMID: 20970431</ref>

	==Biological significance==		==Biological significance==

Marcin Jozef Suskiewicz at 07:04, 17 November 2010

Marcin Jozef Suskiewicz — Wed, 17 Nov 2010 07:04:43 GMT

←Older revision		Revision as of 07:04, 17 November 2010
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	===Ligand binding===		===Ligand binding===
	During the NodS-catalyzed reaction, the chitooligosaccharide substrate is methylated while the methyl donor, S-adenosyl-L-methionine, is transformed into S-adenosyl-L-homocysteine. The latter product is, however, chemically still highly similar to S-adenosyl-L-methionine and hence		During the NodS-catalyzed reaction, the chitooligosaccharide substrate is methylated while the methyl donor, S-adenosyl-L-methionine, is transformed into S-adenosyl-L-homocysteine. The latter product is, however, chemically still highly similar to S-adenosyl-L-methionine and hence
-	<scene name='User:Marcin_Jozef_Suskiewicz/Sandbox_MarcinSuskiewicz/3/1'>the structure of NodS bound to S-adenosyl-L-homocysteine</scene> gives reliable representation of the binding mode of both S-adenosyl-L-homocysteine and, by inference, S-adenosyl-L-methionine to the enzyme. Notice the position of the helix A (the most N-terminal), which was not visible in the apo form, but got structured upon ligand binding; this helix, unlike others, is positioned on top of the β-sheet structure, not on its side, and is in close proximity to the ligand. The <scene name='User:Marcin_Jozef_Suskiewicz/Sandbox_MarcinSuskiewicz/3/2'>S-adenosyl-L-homocysteine</scene>-binding cavity is predominately hydrophobic, but numerous polar interactions are likely to play a role in positioning the ligand in its specific orientation. There are <scene name='User:Marcin_Jozef_Suskiewicz/Sandbox_MarcinSuskiewicz/2/3'>11 polar interactions</scene> between NodS residues and S-adenosyl-L-methionine ligand and around 5-7 additional ones between the water molecules present in the binding pocket and the ligand. The <scene name='User:Marcin_Jozef_Suskiewicz/Sandbox_MarcinSuskiewicz/2/4'>amino group of the homocysteine amino acid moiety is anchored</scene> by the main-chain carbonyl groups of Gly 52 and Ala 114 from loop β1–αC and strand β4, respectively. The <scene name='User:Marcin_Jozef_Suskiewicz/Sandbox_MarcinSuskiewicz/2/5'>carboxy group of the same moiety interacts</scene> with the side chains of the basic amino acid residues Arg 31 and His 32 in helix αB. The <scene name='User:Marcin_Jozef_Suskiewicz/Sandbox_MarcinSuskiewicz/2/7'>hydroxyl groups of the ribose fragment of S-adenosyl-L-homocysteine form</scene> a pair of forked hydrogen bonds with both oxygen atoms of the carboxylic group of Asp 73 and a single hydrogen bond with main-chain nitrogen of Ala 54, Asp 73 being located at the tip of the β2 strand and Ala 54 in loop β1–αC. Finally, <scene name='User:Marcin_Jozef_Suskiewicz/Sandbox_MarcinSuskiewicz/2/8'>the adenine ring of the ligand is interacting</scene> with the main-chain nitrogen of Ile 99 and by the side chain of Asp 98, both from the β3–β4 loop. This adenine ring is also capable of making CH-π interactions with aliphatic side chains of valines 74 and 116. <scene name='User:Marcin_Jozef_Suskiewicz/Sandbox_MarcinSuskiewicz/2/9'>An additional interaction</scene> ~~could~~ potentially be formed between the sulfonium group of the ligand and the π system of Trp 20 when the methyl donor, S-adenosyl-L-methionine is bound instead of the homocysteine derivative. This interaction is likely to contribute to the larger affinity of NodS towards the methyl donor (a substrate) comparing to the homocysteine derivative (a products). The overall positioning of the methyl donor inside the protein is such that it is <scene name='User:Marcin_Jozef_Suskiewicz/Sandbox_MarcinSuskiewicz/4/1'>guarded from the environment</scene>, but the fragment of it where the methyl group of S-adenosyl-L-methionine is located <scene name='User:Marcin_Jozef_Suskiewicz/Sandbox_MarcinSuskiewicz/4/2'>is exposed</scene> to the putative substrate-binding canyon. The canyon is roughly 22 Å long, 10.5 Å wide and 10.5 Å deep. It is located near the N-terminal end of helix αB and the C-terminal end of strand β4. No structure of NodS with the substrate bound is available, but computational docking suggests that this canyon is indeed an energetically favourable binding site, mainly due to a number of polar interactions.<ref>PMID: 20970431</ref>	+	<scene name='User:Marcin_Jozef_Suskiewicz/Sandbox_MarcinSuskiewicz/3/1'>the structure of NodS bound to S-adenosyl-L-homocysteine</scene> gives reliable representation of the binding mode of both S-adenosyl-L-homocysteine and, by inference, S-adenosyl-L-methionine to the enzyme. Notice the position of the helix A (the most N-terminal), which was not visible in the apo form, but got structured upon ligand binding; this helix, unlike others, is positioned on top of the β-sheet structure, not on its side, and is in close proximity to the ligand. There are many other small changes in the structure of ligand-bound NodS when compared to the apo form, mainly around the binding cavity, but the deviations do not exceed 0.9 Å. The <scene name='User:Marcin_Jozef_Suskiewicz/Sandbox_MarcinSuskiewicz/3/2'>S-adenosyl-L-homocysteine</scene>-binding cavity is predominately hydrophobic, but numerous polar interactions are likely to play a role in positioning the ligand in its specific orientation. There are <scene name='User:Marcin_Jozef_Suskiewicz/Sandbox_MarcinSuskiewicz/2/3'>11 polar interactions</scene> between NodS residues and S-adenosyl-L-methionine ligand and around 5-7 additional ones between the water molecules present in the binding pocket and the ligand. The <scene name='User:Marcin_Jozef_Suskiewicz/Sandbox_MarcinSuskiewicz/2/4'>amino group of the homocysteine amino acid moiety is anchored</scene> by the main-chain carbonyl groups of Gly 52 and Ala 114 from loop β1–αC and strand β4, respectively. The <scene name='User:Marcin_Jozef_Suskiewicz/Sandbox_MarcinSuskiewicz/2/5'>carboxy group of the same moiety interacts</scene> with the side chains of the basic amino acid residues Arg 31 and His 32 in helix αB. The <scene name='User:Marcin_Jozef_Suskiewicz/Sandbox_MarcinSuskiewicz/2/7'>hydroxyl groups of the ribose fragment of S-adenosyl-L-homocysteine form</scene> a pair of forked hydrogen bonds with both oxygen atoms of the carboxylic group of Asp 73 and a single hydrogen bond with main-chain nitrogen of Ala 54, Asp 73 being located at the tip of the β2 strand and Ala 54 in loop β1–αC. Finally, <scene name='User:Marcin_Jozef_Suskiewicz/Sandbox_MarcinSuskiewicz/2/8'>the adenine ring of the ligand is interacting</scene> with the main-chain nitrogen of Ile 99 and by the side chain of Asp 98, both from the β3–β4 loop. This adenine ring is also capable of making CH-π interactions with aliphatic side chains of valines 74 and 116. <scene name='User:Marcin_Jozef_Suskiewicz/Sandbox_MarcinSuskiewicz/2/9'>An additional interaction</scene> can potentially be formed between the sulfonium group of the ligand and the π system of Trp 20 when the methyl donor, S-adenosyl-L-methionine is bound instead of the homocysteine derivative. This interaction is likely to contribute to the larger affinity of NodS towards the methyl donor (a substrate) comparing to the homocysteine derivative (a products). The overall positioning of the methyl donor inside the protein is such that it is <scene name='User:Marcin_Jozef_Suskiewicz/Sandbox_MarcinSuskiewicz/4/1'>guarded from the environment</scene>, but the fragment of it where the methyl group of S-adenosyl-L-methionine is located <scene name='User:Marcin_Jozef_Suskiewicz/Sandbox_MarcinSuskiewicz/4/2'>is exposed</scene> to the putative substrate-binding canyon. The canyon is roughly 22 Å long, 10.5 Å wide and 10.5 Å deep. It is located near the N-terminal end of helix αB and the C-terminal end of strand β4. No structure of NodS with the substrate bound is available, but computational docking suggests that this canyon is indeed an energetically favourable binding site, mainly due to a number of polar interactions.<ref>PMID: 20970431</ref>

	</StructureSection>		</StructureSection>

Marcin Jozef Suskiewicz at 06:59, 17 November 2010

Marcin Jozef Suskiewicz — Wed, 17 Nov 2010 06:59:08 GMT

←Older revision		Revision as of 06:59, 17 November 2010
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	===Fold===		===Fold===
	NodS is an S-adenosyl-L-methionine (SAM)-dependent methyltransferase that methylates the deacetylated nitrogen atom at the nonreducing end of the chitooligosaccharide substrate, converting at the same time the S-adenosyl-L-methionine methyl donor into S-adenosyl-L-homocysteine, which is then released as a by-product.<ref>PMID: 7494487</ref>		NodS is an S-adenosyl-L-methionine (SAM)-dependent methyltransferase that methylates the deacetylated nitrogen atom at the nonreducing end of the chitooligosaccharide substrate, converting at the same time the S-adenosyl-L-methionine methyl donor into S-adenosyl-L-homocysteine, which is then released as a by-product.<ref>PMID: 7494487</ref>
-	S-adenosyl-L-methionine-dependent methyltransferases, many of which have been reported to date, methylate a wide variety of substrates and are involved in diverse processes ranging from biosynthetic pathways to gene silencing. Those of them which have been structurally analyzed have been divided into five structural families known as classes I–V, class I, to which NodS belongs, being the most numerous.<ref>PMID: 12826405</ref> Its <scene name='User:Marcin_Jozef_Suskiewicz/Sandbox_MarcinSuskiewicz/1/2'>typical fold</scene> consists of a <scene name='User:Marcin_Jozef_Suskiewicz/Sandbox_MarcinSuskiewicz/1/3'>seven-stranded β-sheet</scene> with a <scene name='User:Marcin_Jozef_Suskiewicz/Sandbox_MarcinSuskiewicz/1/8'>reversed β-hairpin</scene> (residues 182-189) at the C-terminal end of the sheet, between strands β6 and β7. The sheet, which is characterized by a curvature due to the presence of three β-bulges, is surrounded on both sides by <scene name='User:Marcin_Jozef_Suskiewicz/Sandbox_MarcinSuskiewicz/1/5'>α-helices</scene>, forming an <scene name='User:Marcin_Jozef_Suskiewicz/Sandbox_MarcinSuskiewicz/1/2'>α/β/α</scene> folding pattern. In the apo form shown here, only 6 out of 7 helices are visible. In addition to conventional helices, there are also three short, 3<sub>10</sub> helices (not represented as helices), each one-turn-long (residues 19-21, 63-65, 117-119), <scene name='User:Marcin_Jozef_Suskiewicz/Sandbox_MarcinSuskiewicz/1/7'>two of which are visible</scene> in the apo structure. The fact that <scene name='User:Marcin_Jozef_Suskiewicz/Sandbox_MarcinSuskiewicz/1/9'>strand β7 is inserted in an anti-parallel orientation</scene> results in a divergence from a classic Rossmann fold<ref>PMID: 4737475</ref>, to which the structure is otherwise classifiable.	+	S-adenosyl-L-methionine-dependent methyltransferases, many of which have been reported to date, methylate a wide variety of substrates and are involved in diverse processes ranging from biosynthetic pathways to gene silencing. Those of them which have been structurally analyzed have been divided into five structural families known as classes I–V, class I, to which NodS belongs, being the most numerous.<ref>PMID: 12826405</ref> Its <scene name='User:Marcin_Jozef_Suskiewicz/Sandbox_MarcinSuskiewicz/1/2'>typical fold</scene> consists of a <scene name='User:Marcin_Jozef_Suskiewicz/Sandbox_MarcinSuskiewicz/1/3'>seven-stranded β-sheet</scene> (labelled 1-7 beginning from the N-terminus) with a <scene name='User:Marcin_Jozef_Suskiewicz/Sandbox_MarcinSuskiewicz/1/8'>reversed β-hairpin</scene> (residues 182-189) at the C-terminal end of the sheet, between strands β6 and β7. The sheet, which is characterized by a curvature due to the presence of three β-bulges, is surrounded on both sides by <scene name='User:Marcin_Jozef_Suskiewicz/Sandbox_MarcinSuskiewicz/1/5'>α-helices</scene> (labelled A-G beginning from the N-terminus), forming an <scene name='User:Marcin_Jozef_Suskiewicz/Sandbox_MarcinSuskiewicz/1/2'>α/β/α</scene> folding pattern. In the apo form shown here, only 6 out of 7 helices are visible. In addition to conventional helices, there are also three short, 3<sub>10</sub> helices (not represented as helices), each one-turn-long (residues 19-21, 63-65, 117-119), <scene name='User:Marcin_Jozef_Suskiewicz/Sandbox_MarcinSuskiewicz/1/7'>two of which are visible</scene> in the apo structure. The fact that <scene name='User:Marcin_Jozef_Suskiewicz/Sandbox_MarcinSuskiewicz/1/9'>strand β7 is inserted in an anti-parallel orientation</scene> results in a divergence from a classic Rossmann fold<ref>PMID: 4737475</ref>, to which the structure is otherwise classifiable.


	===Ligand binding===		===Ligand binding===
	During the NodS-catalyzed reaction, the chitooligosaccharide substrate is methylated while the methyl donor, S-adenosyl-L-methionine, is transformed into S-adenosyl-L-homocysteine. The latter product is, however, chemically still highly similar to S-adenosyl-L-methionine and hence		During the NodS-catalyzed reaction, the chitooligosaccharide substrate is methylated while the methyl donor, S-adenosyl-L-methionine, is transformed into S-adenosyl-L-homocysteine. The latter product is, however, chemically still highly similar to S-adenosyl-L-methionine and hence
-	<scene name='User:Marcin_Jozef_Suskiewicz/Sandbox_MarcinSuskiewicz/3/1'>the structure of NodS bound to S-adenosyl-L-homocysteine</scene> gives reliable representation of the binding mode of both S-adenosyl-L-homocysteine and, by inference, S-adenosyl-L-methionine to the enzyme. Notice the position of the helix A (the most N-terminal), which was not visible in the apo form, but got structured upon ligand binding; this helix, unlike others, is positioned on top of the β-sheet structure, not on its side, and is in close proximity to the ligand. The <scene name='User:Marcin_Jozef_Suskiewicz/Sandbox_MarcinSuskiewicz/3/2'>S-adenosyl-L-homocysteine</scene>-binding cavity is predominately hydrophobic, but numerous polar interactions are likely to play a role in positioning the ligand in its specific orientation. There are <scene name='User:Marcin_Jozef_Suskiewicz/Sandbox_MarcinSuskiewicz/2/3'>11 polar interactions</scene> between NodS residues and S-adenosyl-L-methionine ligand and around 5-7 additional ones between the water molecules present in the binding pocket and the ligand. The <scene name='User:Marcin_Jozef_Suskiewicz/Sandbox_MarcinSuskiewicz/2/4'>amino group of the homocysteine amino acid moiety is anchored</scene> by the main-chain carbonyl groups of Gly 52 and Ala 114 from loop β1–αC and strand β4, respectively. The <scene name='User:Marcin_Jozef_Suskiewicz/Sandbox_MarcinSuskiewicz/2/5'>carboxy group of the same moiety interacts</scene> with the side chains of the basic amino acid residues Arg 31 and His 32 in helix αB. The <scene name='User:Marcin_Jozef_Suskiewicz/Sandbox_MarcinSuskiewicz/2/7'>hydroxyl groups of the ribose fragment of S-adenosyl-L-homocysteine form</scene> a pair of forked hydrogen bonds with both oxygen atoms of the carboxylic group of Asp 73 and a single hydrogen bond with main-chain nitrogen of Ala 54, Asp 73 being located at the tip of the β2 strand and Ala 54 in loop β1–αC. Finally, <scene name='User:Marcin_Jozef_Suskiewicz/Sandbox_MarcinSuskiewicz/2/8'>the adenine ring of the ligand is interacting</scene> with the main-chain nitrogen of Ile 99 and by the side chain of Asp 98, both from the β3–β4 loop. This adenine ring is also capable of making CH-π interactions with aliphatic side chains of valines 74 and 116. <scene name='User:Marcin_Jozef_Suskiewicz/Sandbox_MarcinSuskiewicz/2/9'>An additional interaction</scene> could potentially be formed between the sulfonium group of the ligand and the π system of Trp 20 when the methyl donor, S-adenosyl-L-methionine is bound instead of the homocysteine derivative. This interaction is likely to contribute to the larger affinity of NodS towards the methyl donor (a substrate) comparing to the homocysteine derivative (a products). The overall positioning of the methyl donor inside the protein is such that it is <scene name='User:Marcin_Jozef_Suskiewicz/Sandbox_MarcinSuskiewicz/4/1'>guarded from the environment</scene>, but the fragment of it where the methyl group of S-adenosyl-L-methionine is located <scene name='User:Marcin_Jozef_Suskiewicz/Sandbox_MarcinSuskiewicz/4/2'>is exposed</scene> to the putative substrate-binding ~~cavity~~.	+	<scene name='User:Marcin_Jozef_Suskiewicz/Sandbox_MarcinSuskiewicz/3/1'>the structure of NodS bound to S-adenosyl-L-homocysteine</scene> gives reliable representation of the binding mode of both S-adenosyl-L-homocysteine and, by inference, S-adenosyl-L-methionine to the enzyme. Notice the position of the helix A (the most N-terminal), which was not visible in the apo form, but got structured upon ligand binding; this helix, unlike others, is positioned on top of the β-sheet structure, not on its side, and is in close proximity to the ligand. The <scene name='User:Marcin_Jozef_Suskiewicz/Sandbox_MarcinSuskiewicz/3/2'>S-adenosyl-L-homocysteine</scene>-binding cavity is predominately hydrophobic, but numerous polar interactions are likely to play a role in positioning the ligand in its specific orientation. There are <scene name='User:Marcin_Jozef_Suskiewicz/Sandbox_MarcinSuskiewicz/2/3'>11 polar interactions</scene> between NodS residues and S-adenosyl-L-methionine ligand and around 5-7 additional ones between the water molecules present in the binding pocket and the ligand. The <scene name='User:Marcin_Jozef_Suskiewicz/Sandbox_MarcinSuskiewicz/2/4'>amino group of the homocysteine amino acid moiety is anchored</scene> by the main-chain carbonyl groups of Gly 52 and Ala 114 from loop β1–αC and strand β4, respectively. The <scene name='User:Marcin_Jozef_Suskiewicz/Sandbox_MarcinSuskiewicz/2/5'>carboxy group of the same moiety interacts</scene> with the side chains of the basic amino acid residues Arg 31 and His 32 in helix αB. The <scene name='User:Marcin_Jozef_Suskiewicz/Sandbox_MarcinSuskiewicz/2/7'>hydroxyl groups of the ribose fragment of S-adenosyl-L-homocysteine form</scene> a pair of forked hydrogen bonds with both oxygen atoms of the carboxylic group of Asp 73 and a single hydrogen bond with main-chain nitrogen of Ala 54, Asp 73 being located at the tip of the β2 strand and Ala 54 in loop β1–αC. Finally, <scene name='User:Marcin_Jozef_Suskiewicz/Sandbox_MarcinSuskiewicz/2/8'>the adenine ring of the ligand is interacting</scene> with the main-chain nitrogen of Ile 99 and by the side chain of Asp 98, both from the β3–β4 loop. This adenine ring is also capable of making CH-π interactions with aliphatic side chains of valines 74 and 116. <scene name='User:Marcin_Jozef_Suskiewicz/Sandbox_MarcinSuskiewicz/2/9'>An additional interaction</scene> could potentially be formed between the sulfonium group of the ligand and the π system of Trp 20 when the methyl donor, S-adenosyl-L-methionine is bound instead of the homocysteine derivative. This interaction is likely to contribute to the larger affinity of NodS towards the methyl donor (a substrate) comparing to the homocysteine derivative (a products). The overall positioning of the methyl donor inside the protein is such that it is <scene name='User:Marcin_Jozef_Suskiewicz/Sandbox_MarcinSuskiewicz/4/1'>guarded from the environment</scene>, but the fragment of it where the methyl group of S-adenosyl-L-methionine is located <scene name='User:Marcin_Jozef_Suskiewicz/Sandbox_MarcinSuskiewicz/4/2'>is exposed</scene> to the putative substrate-binding canyon. The canyon is roughly 22 Å long, 10.5 Å wide and 10.5 Å deep. It is located near the N-terminal end of helix αB and the C-terminal end of strand β4. No structure of NodS with the substrate bound is available, but computational docking suggests that this canyon is indeed an energetically favourable binding site, mainly due to a number of polar interactions.<ref>PMID: 20970431</ref>

	</StructureSection>		</StructureSection>

Marcin Jozef Suskiewicz at 06:51, 17 November 2010

Marcin Jozef Suskiewicz — Wed, 17 Nov 2010 06:51:00 GMT

←Older revision		Revision as of 06:51, 17 November 2010
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	==Reference==		==Reference==
	<references/>		<references/>
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-
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-	Copy and paste the following line where you want the scene link to appear (scroll down if needed) and edit the TextToBeDisplayed:
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-	<scene name='User:Marcin_Jozef_Suskiewicz/Sandbox_MarcinSuskiewicz/3/3'>TextToBeDisplayed</scene>

Marcin Jozef Suskiewicz at 06:48, 17 November 2010

Marcin Jozef Suskiewicz — Wed, 17 Nov 2010 06:48:31 GMT

←Older revision		Revision as of 06:48, 17 November 2010
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	===Ligand binding===		===Ligand binding===
	During the NodS-catalyzed reaction, the chitooligosaccharide substrate is methylated while the methyl donor, S-adenosyl-L-methionine, is transformed into S-adenosyl-L-homocysteine. The latter product is, however, chemically still highly similar to S-adenosyl-L-methionine and hence		During the NodS-catalyzed reaction, the chitooligosaccharide substrate is methylated while the methyl donor, S-adenosyl-L-methionine, is transformed into S-adenosyl-L-homocysteine. The latter product is, however, chemically still highly similar to S-adenosyl-L-methionine and hence
-	<scene name='User:Marcin_Jozef_Suskiewicz/Sandbox_MarcinSuskiewicz/3/1'>the structure of NodS bound to S-adenosyl-L-homocysteine</scene> gives reliable representation of the binding mode of both S-adenosyl-L-homocysteine and, by inference, S-adenosyl-L-methionine to the enzyme. Notice the position of the helix A (the most N-terminal), which was not visible in the apo form, but got structured upon ligand binding; this helix, unlike others, is positioned on top of the β-sheet structure, not on its side, and is in close proximity to the ligand. The <scene name='User:Marcin_Jozef_Suskiewicz/Sandbox_MarcinSuskiewicz/3/2'>S-adenosyl-L-homocysteine</scene>-binding cavity is predominately hydrophobic, but numerous polar interactions are likely to play a role in positioning the ligand in its specific orientation. There are <scene name='User:Marcin_Jozef_Suskiewicz/Sandbox_MarcinSuskiewicz/2/3'>11 polar interactions</scene> between NodS residues and S-adenosyl-L-methionine ligand and around 5-7 additional ones between the water molecules present in the binding pocket and the ligand. The <scene name='User:Marcin_Jozef_Suskiewicz/Sandbox_MarcinSuskiewicz/2/4'>amino group of the homocysteine amino acid moiety is anchored</scene> by the main-chain carbonyl groups of Gly 52 and Ala 114 from loop β1–αC and strand β4, respectively. The <scene name='User:Marcin_Jozef_Suskiewicz/Sandbox_MarcinSuskiewicz/2/5'>carboxy group of the same moiety interacts</scene> with the side chains of the basic amino acid residues Arg 31 and His 32 in helix αB. The <scene name='User:Marcin_Jozef_Suskiewicz/Sandbox_MarcinSuskiewicz/2/7'>hydroxyl groups of the ribose fragment of S-adenosyl-L-homocysteine form</scene> a pair of forked hydrogen bonds with both oxygen atoms of the carboxylic group of Asp 73 and a single hydrogen bond with main-chain nitrogen of Ala 54, Asp 73 being located at the tip of the β2 strand and Ala 54 in loop β1–αC. Finally, <scene name='User:Marcin_Jozef_Suskiewicz/Sandbox_MarcinSuskiewicz/2/8'>the adenine ring of the ligand is interacting</scene> with the main-chain nitrogen of Ile 99 and by the side chain of Asp 98, both from the β3–β4 loop. This adenine ring is also capable of making CH-π interactions with aliphatic side chains of valines 74 and 116. <scene name='User:Marcin_Jozef_Suskiewicz/Sandbox_MarcinSuskiewicz/2/9'>An additional interaction</scene> could potentially be formed between the sulfonium group of the ligand and the π system of Trp 20 when the methyl donor, S-adenosyl-L-methionine is bound instead of the homocysteine derivative. This interaction is likely to contribute to the larger affinity of NodS towards the methyl donor (a substrate) comparing to the homocysteine derivative (a products). The overall positioning of the methyl donor is such that it is <scene name='User:Marcin_Jozef_Suskiewicz/Sandbox_MarcinSuskiewicz/4/1'>guarded from the environment</scene>, but the fragment of it where the <scene name='User:Marcin_Jozef_Suskiewicz/Sandbox_MarcinSuskiewicz/4/2'>~~methyl group~~ is exposed</scene> to the putative substrate-binding cavity.	+	<scene name='User:Marcin_Jozef_Suskiewicz/Sandbox_MarcinSuskiewicz/3/1'>the structure of NodS bound to S-adenosyl-L-homocysteine</scene> gives reliable representation of the binding mode of both S-adenosyl-L-homocysteine and, by inference, S-adenosyl-L-methionine to the enzyme. Notice the position of the helix A (the most N-terminal), which was not visible in the apo form, but got structured upon ligand binding; this helix, unlike others, is positioned on top of the β-sheet structure, not on its side, and is in close proximity to the ligand. The <scene name='User:Marcin_Jozef_Suskiewicz/Sandbox_MarcinSuskiewicz/3/2'>S-adenosyl-L-homocysteine</scene>-binding cavity is predominately hydrophobic, but numerous polar interactions are likely to play a role in positioning the ligand in its specific orientation. There are <scene name='User:Marcin_Jozef_Suskiewicz/Sandbox_MarcinSuskiewicz/2/3'>11 polar interactions</scene> between NodS residues and S-adenosyl-L-methionine ligand and around 5-7 additional ones between the water molecules present in the binding pocket and the ligand. The <scene name='User:Marcin_Jozef_Suskiewicz/Sandbox_MarcinSuskiewicz/2/4'>amino group of the homocysteine amino acid moiety is anchored</scene> by the main-chain carbonyl groups of Gly 52 and Ala 114 from loop β1–αC and strand β4, respectively. The <scene name='User:Marcin_Jozef_Suskiewicz/Sandbox_MarcinSuskiewicz/2/5'>carboxy group of the same moiety interacts</scene> with the side chains of the basic amino acid residues Arg 31 and His 32 in helix αB. The <scene name='User:Marcin_Jozef_Suskiewicz/Sandbox_MarcinSuskiewicz/2/7'>hydroxyl groups of the ribose fragment of S-adenosyl-L-homocysteine form</scene> a pair of forked hydrogen bonds with both oxygen atoms of the carboxylic group of Asp 73 and a single hydrogen bond with main-chain nitrogen of Ala 54, Asp 73 being located at the tip of the β2 strand and Ala 54 in loop β1–αC. Finally, <scene name='User:Marcin_Jozef_Suskiewicz/Sandbox_MarcinSuskiewicz/2/8'>the adenine ring of the ligand is interacting</scene> with the main-chain nitrogen of Ile 99 and by the side chain of Asp 98, both from the β3–β4 loop. This adenine ring is also capable of making CH-π interactions with aliphatic side chains of valines 74 and 116. <scene name='User:Marcin_Jozef_Suskiewicz/Sandbox_MarcinSuskiewicz/2/9'>An additional interaction</scene> could potentially be formed between the sulfonium group of the ligand and the π system of Trp 20 when the methyl donor, S-adenosyl-L-methionine is bound instead of the homocysteine derivative. This interaction is likely to contribute to the larger affinity of NodS towards the methyl donor (a substrate) comparing to the homocysteine derivative (a products). The overall positioning of the methyl donor inside the protein is such that it is <scene name='User:Marcin_Jozef_Suskiewicz/Sandbox_MarcinSuskiewicz/4/1'>guarded from the environment</scene>, but the fragment of it where the methyl group of S-adenosyl-L-methionine is located <scene name='User:Marcin_Jozef_Suskiewicz/Sandbox_MarcinSuskiewicz/4/2'>is exposed</scene> to the putative substrate-binding cavity.

	</StructureSection>		</StructureSection>

Marcin Jozef Suskiewicz at 06:46, 17 November 2010

Marcin Jozef Suskiewicz — Wed, 17 Nov 2010 06:46:46 GMT

←Older revision		Revision as of 06:46, 17 November 2010
Line 23:		Line 23:
	===Ligand binding===		===Ligand binding===
	During the NodS-catalyzed reaction, the chitooligosaccharide substrate is methylated while the methyl donor, S-adenosyl-L-methionine, is transformed into S-adenosyl-L-homocysteine. The latter product is, however, chemically still highly similar to S-adenosyl-L-methionine and hence		During the NodS-catalyzed reaction, the chitooligosaccharide substrate is methylated while the methyl donor, S-adenosyl-L-methionine, is transformed into S-adenosyl-L-homocysteine. The latter product is, however, chemically still highly similar to S-adenosyl-L-methionine and hence
-	<scene name='User:Marcin_Jozef_Suskiewicz/Sandbox_MarcinSuskiewicz/3/1'>the structure of NodS bound to S-adenosyl-L-homocysteine</scene> gives reliable representation of the binding mode of both S-adenosyl-L-homocysteine and, by inference, S-adenosyl-L-methionine to the enzyme. Notice the position of the helix A (the most N-terminal), which was not visible in the apo form, but got structured upon ligand binding; this helix, unlike others, is positioned on top of the β-sheet structure, not on its side, and is in close proximity to the ligand. The <scene name='User:Marcin_Jozef_Suskiewicz/Sandbox_MarcinSuskiewicz/3/2'>S-adenosyl-L-homocysteine</scene>-binding cavity is predominately hydrophobic, but numerous polar interactions are likely to play a role in positioning the ligand in its specific orientation. There are <scene name='User:Marcin_Jozef_Suskiewicz/Sandbox_MarcinSuskiewicz/2/3'>11 polar interactions</scene> between NodS residues and S-adenosyl-L-methionine ligand and around 5-7 additional ones between the water molecules present in the binding pocket and the ligand. The <scene name='User:Marcin_Jozef_Suskiewicz/Sandbox_MarcinSuskiewicz/2/4'>amino group of the homocysteine amino acid moiety is anchored</scene> by the main-chain carbonyl groups of Gly 52 and Ala 114 from loop β1–αC and strand β4, respectively. The <scene name='User:Marcin_Jozef_Suskiewicz/Sandbox_MarcinSuskiewicz/2/5'>carboxy group of the same moiety interacts</scene> with the side chains of the basic amino acid residues Arg 31 and His 32 in helix αB. The <scene name='User:Marcin_Jozef_Suskiewicz/Sandbox_MarcinSuskiewicz/2/7'>hydroxyl groups of the ribose fragment of S-adenosyl-L-homocysteine form</scene> a pair of forked hydrogen bonds with both oxygen atoms of the carboxylic group of Asp 73 and a single hydrogen bond with main-chain nitrogen of Ala 54, Asp 73 being located at the tip of the β2 strand and Ala 54 in loop β1–αC. Finally, <scene name='User:Marcin_Jozef_Suskiewicz/Sandbox_MarcinSuskiewicz/2/8'>the adenine ring of the ligand is interacting</scene> with the main-chain nitrogen of Ile 99 and by the side chain of Asp 98, both from the β3–β4 loop. This adenine ring is also capable of making CH-π interactions with aliphatic side chains of valines 74 and 116. <scene name='User:Marcin_Jozef_Suskiewicz/Sandbox_MarcinSuskiewicz/2/9'>An additional interaction</scene> could potentially be formed between the sulfonium group of the ligand and the π system of Trp 20 when the methyl donor, S-adenosyl-L-methionine is bound instead of the homocysteine derivative. This interaction is likely to contribute to the larger affinity of NodS towards the methyl donor (a substrate) comparing to the homocysteine derivative (a products).	+	<scene name='User:Marcin_Jozef_Suskiewicz/Sandbox_MarcinSuskiewicz/3/1'>the structure of NodS bound to S-adenosyl-L-homocysteine</scene> gives reliable representation of the binding mode of both S-adenosyl-L-homocysteine and, by inference, S-adenosyl-L-methionine to the enzyme. Notice the position of the helix A (the most N-terminal), which was not visible in the apo form, but got structured upon ligand binding; this helix, unlike others, is positioned on top of the β-sheet structure, not on its side, and is in close proximity to the ligand. The <scene name='User:Marcin_Jozef_Suskiewicz/Sandbox_MarcinSuskiewicz/3/2'>S-adenosyl-L-homocysteine</scene>-binding cavity is predominately hydrophobic, but numerous polar interactions are likely to play a role in positioning the ligand in its specific orientation. There are <scene name='User:Marcin_Jozef_Suskiewicz/Sandbox_MarcinSuskiewicz/2/3'>11 polar interactions</scene> between NodS residues and S-adenosyl-L-methionine ligand and around 5-7 additional ones between the water molecules present in the binding pocket and the ligand. The <scene name='User:Marcin_Jozef_Suskiewicz/Sandbox_MarcinSuskiewicz/2/4'>amino group of the homocysteine amino acid moiety is anchored</scene> by the main-chain carbonyl groups of Gly 52 and Ala 114 from loop β1–αC and strand β4, respectively. The <scene name='User:Marcin_Jozef_Suskiewicz/Sandbox_MarcinSuskiewicz/2/5'>carboxy group of the same moiety interacts</scene> with the side chains of the basic amino acid residues Arg 31 and His 32 in helix αB. The <scene name='User:Marcin_Jozef_Suskiewicz/Sandbox_MarcinSuskiewicz/2/7'>hydroxyl groups of the ribose fragment of S-adenosyl-L-homocysteine form</scene> a pair of forked hydrogen bonds with both oxygen atoms of the carboxylic group of Asp 73 and a single hydrogen bond with main-chain nitrogen of Ala 54, Asp 73 being located at the tip of the β2 strand and Ala 54 in loop β1–αC. Finally, <scene name='User:Marcin_Jozef_Suskiewicz/Sandbox_MarcinSuskiewicz/2/8'>the adenine ring of the ligand is interacting</scene> with the main-chain nitrogen of Ile 99 and by the side chain of Asp 98, both from the β3–β4 loop. This adenine ring is also capable of making CH-π interactions with aliphatic side chains of valines 74 and 116. <scene name='User:Marcin_Jozef_Suskiewicz/Sandbox_MarcinSuskiewicz/2/9'>An additional interaction</scene> could potentially be formed between the sulfonium group of the ligand and the π system of Trp 20 when the methyl donor, S-adenosyl-L-methionine is bound instead of the homocysteine derivative. This interaction is likely to contribute to the larger affinity of NodS towards the methyl donor (a substrate) comparing to the homocysteine derivative (a products). The overall positioning of the methyl donor is such that it is <scene name='User:Marcin_Jozef_Suskiewicz/Sandbox_MarcinSuskiewicz/4/1'>guarded from the environment</scene>, but the fragment of it where the <scene name='User:Marcin_Jozef_Suskiewicz/Sandbox_MarcinSuskiewicz/4/2'>methyl group is exposed</scene> to the putative substrate-binding cavity.

	</StructureSection>		</StructureSection>

Marcin Jozef Suskiewicz at 06:40, 17 November 2010

Marcin Jozef Suskiewicz — Wed, 17 Nov 2010 06:40:40 GMT

←Older revision		Revision as of 06:40, 17 November 2010
Line 23:		Line 23:
	===Ligand binding===		===Ligand binding===
	During the NodS-catalyzed reaction, the chitooligosaccharide substrate is methylated while the methyl donor, S-adenosyl-L-methionine, is transformed into S-adenosyl-L-homocysteine. The latter product is, however, chemically still highly similar to S-adenosyl-L-methionine and hence		During the NodS-catalyzed reaction, the chitooligosaccharide substrate is methylated while the methyl donor, S-adenosyl-L-methionine, is transformed into S-adenosyl-L-homocysteine. The latter product is, however, chemically still highly similar to S-adenosyl-L-methionine and hence
-	<scene name='User:Marcin_Jozef_Suskiewicz/Sandbox_MarcinSuskiewicz/3/1'>the structure of NodS bound to S-adenosyl-L-homocysteine</scene> gives reliable representation of the binding mode of both ~~<scene name='User:Marcin_Jozef_Suskiewicz/Sandbox_MarcinSuskiewicz/3/2'>~~S-adenosyl-L-homocysteine~~</scene>~~ and, by inference, S-adenosyl-L-methionine to the enzyme. Notice the position of the helix A (the most N-terminal), which was not visible in the apo form, but got structured upon ligand binding; this helix, unlike others, is positioned on top of the β-sheet structure, not on its side, and is in close proximity to the ligand. The ~~ligand~~-binding cavity is predominately hydrophobic, but numerous polar interactions are likely to play a role in positioning the ligand in its specific orientation. There are <scene name='User:Marcin_Jozef_Suskiewicz/Sandbox_MarcinSuskiewicz/2/3'>11 polar interactions</scene> between NodS residues and S-adenosyl-L-methionine ligand and around 5-7 additional ones between the water molecules present in the binding pocket and the ligand. The <scene name='User:Marcin_Jozef_Suskiewicz/Sandbox_MarcinSuskiewicz/2/4'>amino group of the homocysteine amino acid moiety is anchored</scene> by the main-chain carbonyl groups of Gly 52 and Ala 114 from loop β1–αC and strand β4, respectively. The <scene name='User:Marcin_Jozef_Suskiewicz/Sandbox_MarcinSuskiewicz/2/5'>carboxy group of the same moiety interacts</scene> with the side chains of the basic amino acid residues Arg 31 and His 32 in helix αB. The <scene name='User:Marcin_Jozef_Suskiewicz/Sandbox_MarcinSuskiewicz/2/7'>hydroxyl groups of the ribose fragment of S-adenosyl-L-homocysteine form</scene> a pair of forked hydrogen bonds with both oxygen atoms of the carboxylic group of Asp 73 and a single hydrogen bond with main-chain nitrogen of Ala 54, Asp 73 being located at the tip of the β2 strand and Ala 54 in loop β1–αC. Finally, <scene name='User:Marcin_Jozef_Suskiewicz/Sandbox_MarcinSuskiewicz/2/8'>the adenine ring of the ligand is interacting</scene> with the main-chain nitrogen of Ile 99 and by the side chain of Asp 98, both from the β3–β4 loop. This adenine ring is also capable of making CH-π interactions with aliphatic side chains of valines 74 and 116. <scene name='User:Marcin_Jozef_Suskiewicz/Sandbox_MarcinSuskiewicz/2/9'>An additional interaction</scene> could potentially be formed between the sulfonium group of the ligand and the π system of Trp 20 when the methyl donor, S-adenosyl-L-methionine is bound instead of the homocysteine derivative. This interaction is likely to contribute to the larger affinity of NodS towards the methyl donor (a substrate) comparing to the homocysteine derivative (a products).	+	<scene name='User:Marcin_Jozef_Suskiewicz/Sandbox_MarcinSuskiewicz/3/1'>the structure of NodS bound to S-adenosyl-L-homocysteine</scene> gives reliable representation of the binding mode of both S-adenosyl-L-homocysteine and, by inference, S-adenosyl-L-methionine to the enzyme. Notice the position of the helix A (the most N-terminal), which was not visible in the apo form, but got structured upon ligand binding; this helix, unlike others, is positioned on top of the β-sheet structure, not on its side, and is in close proximity to the ligand. The <scene name='User:Marcin_Jozef_Suskiewicz/Sandbox_MarcinSuskiewicz/3/2'>S-adenosyl-L-homocysteine</scene>-binding cavity is predominately hydrophobic, but numerous polar interactions are likely to play a role in positioning the ligand in its specific orientation. There are <scene name='User:Marcin_Jozef_Suskiewicz/Sandbox_MarcinSuskiewicz/2/3'>11 polar interactions</scene> between NodS residues and S-adenosyl-L-methionine ligand and around 5-7 additional ones between the water molecules present in the binding pocket and the ligand. The <scene name='User:Marcin_Jozef_Suskiewicz/Sandbox_MarcinSuskiewicz/2/4'>amino group of the homocysteine amino acid moiety is anchored</scene> by the main-chain carbonyl groups of Gly 52 and Ala 114 from loop β1–αC and strand β4, respectively. The <scene name='User:Marcin_Jozef_Suskiewicz/Sandbox_MarcinSuskiewicz/2/5'>carboxy group of the same moiety interacts</scene> with the side chains of the basic amino acid residues Arg 31 and His 32 in helix αB. The <scene name='User:Marcin_Jozef_Suskiewicz/Sandbox_MarcinSuskiewicz/2/7'>hydroxyl groups of the ribose fragment of S-adenosyl-L-homocysteine form</scene> a pair of forked hydrogen bonds with both oxygen atoms of the carboxylic group of Asp 73 and a single hydrogen bond with main-chain nitrogen of Ala 54, Asp 73 being located at the tip of the β2 strand and Ala 54 in loop β1–αC. Finally, <scene name='User:Marcin_Jozef_Suskiewicz/Sandbox_MarcinSuskiewicz/2/8'>the adenine ring of the ligand is interacting</scene> with the main-chain nitrogen of Ile 99 and by the side chain of Asp 98, both from the β3–β4 loop. This adenine ring is also capable of making CH-π interactions with aliphatic side chains of valines 74 and 116. <scene name='User:Marcin_Jozef_Suskiewicz/Sandbox_MarcinSuskiewicz/2/9'>An additional interaction</scene> could potentially be formed between the sulfonium group of the ligand and the π system of Trp 20 when the methyl donor, S-adenosyl-L-methionine is bound instead of the homocysteine derivative. This interaction is likely to contribute to the larger affinity of NodS towards the methyl donor (a substrate) comparing to the homocysteine derivative (a products).

	</StructureSection>		</StructureSection>

Marcin Jozef Suskiewicz at 06:39, 17 November 2010

Marcin Jozef Suskiewicz — Wed, 17 Nov 2010 06:39:15 GMT

←Older revision		Revision as of 06:39, 17 November 2010
Line 23:		Line 23:
	===Ligand binding===		===Ligand binding===
	During the NodS-catalyzed reaction, the chitooligosaccharide substrate is methylated while the methyl donor, S-adenosyl-L-methionine, is transformed into S-adenosyl-L-homocysteine. The latter product is, however, chemically still highly similar to S-adenosyl-L-methionine and hence		During the NodS-catalyzed reaction, the chitooligosaccharide substrate is methylated while the methyl donor, S-adenosyl-L-methionine, is transformed into S-adenosyl-L-homocysteine. The latter product is, however, chemically still highly similar to S-adenosyl-L-methionine and hence
-	<scene name='User:Marcin_Jozef_Suskiewicz/Sandbox_MarcinSuskiewicz/3/1'>the structure of NodS bound to S-adenosyl-L-homocysteine</scene> gives reliable representation of the binding mode of both <scene name='User:Marcin_Jozef_Suskiewicz/Sandbox_MarcinSuskiewicz/3/2'>S-adenosyl-L-homocysteine</scene> and, by inference, S-adenosyl-L-methionine to the enzyme~~. The ligand-binding cavity is predominately hydrophobic, but numerous polar interactions are likely to play a role in positioning the ligand in its specific orientation~~. Notice the position of the helix A (the most N-terminal), which was not visible in the apo form, but got structured upon ligand binding; this helix, unlike others, is positioned on top of the β-sheet structure, not on its side, and is in close proximity to the ligand. There are <scene name='User:Marcin_Jozef_Suskiewicz/Sandbox_MarcinSuskiewicz/2/3'>11 polar interactions</scene> between NodS residues and S-adenosyl-L-methionine ligand and around 5-7 additional ones between the water molecules present in the binding pocket and the ligand. The <scene name='User:Marcin_Jozef_Suskiewicz/Sandbox_MarcinSuskiewicz/2/4'>amino group of the homocysteine amino acid moiety is anchored</scene> by the main-chain carbonyl groups of Gly 52 and Ala 114 from loop β1–αC and strand β4, respectively. The <scene name='User:Marcin_Jozef_Suskiewicz/Sandbox_MarcinSuskiewicz/2/5'>carboxy group of the same moiety interacts</scene> with the side chains of the basic amino acid residues Arg 31 and His 32 in helix αB. The <scene name='User:Marcin_Jozef_Suskiewicz/Sandbox_MarcinSuskiewicz/2/7'>hydroxyl groups of the ribose fragment of S-adenosyl-L-homocysteine form</scene> a pair of forked hydrogen bonds with both oxygen atoms of the carboxylic group of Asp 73 and a single hydrogen bond with main-chain nitrogen of Ala 54, Asp 73 being located at the tip of the β2 strand and Ala 54 in loop β1–αC. Finally, <scene name='User:Marcin_Jozef_Suskiewicz/Sandbox_MarcinSuskiewicz/2/8'>the adenine ring of the ligand is interacting</scene> with the main-chain nitrogen of Ile 99 and by the side chain of Asp 98, both from the β3–β4 loop. This adenine ring is also capable of making CH-π interactions with aliphatic side chains of valines 74 and 116. <scene name='User:Marcin_Jozef_Suskiewicz/Sandbox_MarcinSuskiewicz/2/9'>An additional interaction</scene> could potentially be formed between the sulfonium group of the ligand and the π system of Trp 20 when the methyl donor, S-adenosyl-L-methionine is bound instead of the homocysteine derivative. This interaction is likely to contribute to the larger affinity of NodS towards the methyl donor (a substrate) comparing to the homocysteine derivative (a products).	+	<scene name='User:Marcin_Jozef_Suskiewicz/Sandbox_MarcinSuskiewicz/3/1'>the structure of NodS bound to S-adenosyl-L-homocysteine</scene> gives reliable representation of the binding mode of both <scene name='User:Marcin_Jozef_Suskiewicz/Sandbox_MarcinSuskiewicz/3/2'>S-adenosyl-L-homocysteine</scene> and, by inference, S-adenosyl-L-methionine to the enzyme. Notice the position of the helix A (the most N-terminal), which was not visible in the apo form, but got structured upon ligand binding; this helix, unlike others, is positioned on top of the β-sheet structure, not on its side, and is in close proximity to the ligand. The ligand-binding cavity is predominately hydrophobic, but numerous polar interactions are likely to play a role in positioning the ligand in its specific orientation. There are <scene name='User:Marcin_Jozef_Suskiewicz/Sandbox_MarcinSuskiewicz/2/3'>11 polar interactions</scene> between NodS residues and S-adenosyl-L-methionine ligand and around 5-7 additional ones between the water molecules present in the binding pocket and the ligand. The <scene name='User:Marcin_Jozef_Suskiewicz/Sandbox_MarcinSuskiewicz/2/4'>amino group of the homocysteine amino acid moiety is anchored</scene> by the main-chain carbonyl groups of Gly 52 and Ala 114 from loop β1–αC and strand β4, respectively. The <scene name='User:Marcin_Jozef_Suskiewicz/Sandbox_MarcinSuskiewicz/2/5'>carboxy group of the same moiety interacts</scene> with the side chains of the basic amino acid residues Arg 31 and His 32 in helix αB. The <scene name='User:Marcin_Jozef_Suskiewicz/Sandbox_MarcinSuskiewicz/2/7'>hydroxyl groups of the ribose fragment of S-adenosyl-L-homocysteine form</scene> a pair of forked hydrogen bonds with both oxygen atoms of the carboxylic group of Asp 73 and a single hydrogen bond with main-chain nitrogen of Ala 54, Asp 73 being located at the tip of the β2 strand and Ala 54 in loop β1–αC. Finally, <scene name='User:Marcin_Jozef_Suskiewicz/Sandbox_MarcinSuskiewicz/2/8'>the adenine ring of the ligand is interacting</scene> with the main-chain nitrogen of Ile 99 and by the side chain of Asp 98, both from the β3–β4 loop. This adenine ring is also capable of making CH-π interactions with aliphatic side chains of valines 74 and 116. <scene name='User:Marcin_Jozef_Suskiewicz/Sandbox_MarcinSuskiewicz/2/9'>An additional interaction</scene> could potentially be formed between the sulfonium group of the ligand and the π system of Trp 20 when the methyl donor, S-adenosyl-L-methionine is bound instead of the homocysteine derivative. This interaction is likely to contribute to the larger affinity of NodS towards the methyl donor (a substrate) comparing to the homocysteine derivative (a products).

	</StructureSection>		</StructureSection>

Marcin Jozef Suskiewicz at 06:37, 17 November 2010

Marcin Jozef Suskiewicz — Wed, 17 Nov 2010 06:37:30 GMT

←Older revision		Revision as of 06:37, 17 November 2010
Line 23:		Line 23:
	===Ligand binding===		===Ligand binding===
	During the NodS-catalyzed reaction, the chitooligosaccharide substrate is methylated while the methyl donor, S-adenosyl-L-methionine, is transformed into S-adenosyl-L-homocysteine. The latter product is, however, chemically still highly similar to S-adenosyl-L-methionine and hence		During the NodS-catalyzed reaction, the chitooligosaccharide substrate is methylated while the methyl donor, S-adenosyl-L-methionine, is transformed into S-adenosyl-L-homocysteine. The latter product is, however, chemically still highly similar to S-adenosyl-L-methionine and hence
-	<scene name='User:Marcin_Jozef_Suskiewicz/Sandbox_MarcinSuskiewicz/3/1'>the structure of NodS bound to S-adenosyl-L-homocysteine</scene> gives reliable representation of the binding mode of both <scene name='User:Marcin_Jozef_Suskiewicz/Sandbox_MarcinSuskiewicz/3/2'>S-adenosyl-L-homocysteine</scene> and S-adenosyl-L-methionine to the enzyme. The ligand-binding cavity is predominately hydrophobic, but numerous polar interactions are likely to play a role in positioning the ligand in its specific orientation. There are <scene name='User:Marcin_Jozef_Suskiewicz/Sandbox_MarcinSuskiewicz/2/3'>11 polar interactions</scene> between NodS residues and S-adenosyl-L-methionine ligand and around 5-7 additional ones between the water molecules present in the binding pocket and the ligand. The <scene name='User:Marcin_Jozef_Suskiewicz/Sandbox_MarcinSuskiewicz/2/4'>amino group of the homocysteine amino acid moiety is anchored</scene> by the main-chain carbonyl groups of Gly 52 and Ala 114 from loop β1–αC and strand β4, respectively. The <scene name='User:Marcin_Jozef_Suskiewicz/Sandbox_MarcinSuskiewicz/2/5'>carboxy group of the same moiety interacts</scene> with the side chains of the basic amino acid residues Arg 31 and His 32 in helix αB. The <scene name='User:Marcin_Jozef_Suskiewicz/Sandbox_MarcinSuskiewicz/2/7'>hydroxyl groups of the ribose fragment of S-adenosyl-L-homocysteine form</scene> a pair of forked hydrogen bonds with both oxygen atoms of the carboxylic group of Asp 73 and a single hydrogen bond with main-chain nitrogen of Ala 54, Asp 73 being located at the tip of the β2 strand and Ala 54 in loop β1–αC. Finally, <scene name='User:Marcin_Jozef_Suskiewicz/Sandbox_MarcinSuskiewicz/2/8'>the adenine ring of the ligand is interacting</scene> with the main-chain nitrogen of Ile 99 and by the side chain of Asp 98, both from the β3–β4 loop. This adenine ring is also capable of making CH-π interactions with aliphatic side chains of valines 74 and 116. <scene name='User:Marcin_Jozef_Suskiewicz/Sandbox_MarcinSuskiewicz/2/9'>An additional interaction</scene> could potentially be formed between the sulfonium group of the ligand and the π system of Trp 20 when the methyl donor, S-adenosyl-L-methionine is bound instead of the homocysteine derivative. This interaction is likely to contribute to the larger affinity of NodS towards the methyl donor (a substrate) comparing to the homocysteine derivative (a products).	+	<scene name='User:Marcin_Jozef_Suskiewicz/Sandbox_MarcinSuskiewicz/3/1'>the structure of NodS bound to S-adenosyl-L-homocysteine</scene> gives reliable representation of the binding mode of both <scene name='User:Marcin_Jozef_Suskiewicz/Sandbox_MarcinSuskiewicz/3/2'>S-adenosyl-L-homocysteine</scene> and, by inference, S-adenosyl-L-methionine to the enzyme. The ligand-binding cavity is predominately hydrophobic, but numerous polar interactions are likely to play a role in positioning the ligand in its specific orientation. Notice the position of the helix A (the most N-terminal), which was not visible in the apo form, but got structured upon ligand binding; this helix, unlike others, is positioned on top of the β-sheet structure, not on its side, and is in close proximity to the ligand. There are <scene name='User:Marcin_Jozef_Suskiewicz/Sandbox_MarcinSuskiewicz/2/3'>11 polar interactions</scene> between NodS residues and S-adenosyl-L-methionine ligand and around 5-7 additional ones between the water molecules present in the binding pocket and the ligand. The <scene name='User:Marcin_Jozef_Suskiewicz/Sandbox_MarcinSuskiewicz/2/4'>amino group of the homocysteine amino acid moiety is anchored</scene> by the main-chain carbonyl groups of Gly 52 and Ala 114 from loop β1–αC and strand β4, respectively. The <scene name='User:Marcin_Jozef_Suskiewicz/Sandbox_MarcinSuskiewicz/2/5'>carboxy group of the same moiety interacts</scene> with the side chains of the basic amino acid residues Arg 31 and His 32 in helix αB. The <scene name='User:Marcin_Jozef_Suskiewicz/Sandbox_MarcinSuskiewicz/2/7'>hydroxyl groups of the ribose fragment of S-adenosyl-L-homocysteine form</scene> a pair of forked hydrogen bonds with both oxygen atoms of the carboxylic group of Asp 73 and a single hydrogen bond with main-chain nitrogen of Ala 54, Asp 73 being located at the tip of the β2 strand and Ala 54 in loop β1–αC. Finally, <scene name='User:Marcin_Jozef_Suskiewicz/Sandbox_MarcinSuskiewicz/2/8'>the adenine ring of the ligand is interacting</scene> with the main-chain nitrogen of Ile 99 and by the side chain of Asp 98, both from the β3–β4 loop. This adenine ring is also capable of making CH-π interactions with aliphatic side chains of valines 74 and 116. <scene name='User:Marcin_Jozef_Suskiewicz/Sandbox_MarcinSuskiewicz/2/9'>An additional interaction</scene> could potentially be formed between the sulfonium group of the ligand and the π system of Trp 20 when the methyl donor, S-adenosyl-L-methionine is bound instead of the homocysteine derivative. This interaction is likely to contribute to the larger affinity of NodS towards the methyl donor (a substrate) comparing to the homocysteine derivative (a products).

	</StructureSection>		</StructureSection>

Marcin Jozef Suskiewicz at 06:31, 17 November 2010

Marcin Jozef Suskiewicz — Wed, 17 Nov 2010 06:31:10 GMT

←Older revision		Revision as of 06:31, 17 November 2010
Line 23:		Line 23:
	===Ligand binding===		===Ligand binding===
	During the NodS-catalyzed reaction, the chitooligosaccharide substrate is methylated while the methyl donor, S-adenosyl-L-methionine, is transformed into S-adenosyl-L-homocysteine. The latter product is, however, chemically still highly similar to S-adenosyl-L-methionine and hence		During the NodS-catalyzed reaction, the chitooligosaccharide substrate is methylated while the methyl donor, S-adenosyl-L-methionine, is transformed into S-adenosyl-L-homocysteine. The latter product is, however, chemically still highly similar to S-adenosyl-L-methionine and hence
-	<scene name='User:Marcin_Jozef_Suskiewicz/Sandbox_MarcinSuskiewicz/3/1'>the structure of NodS bound to S-adenosyl-L-homocysteine</scene> gives reliable representation of the binding mode of both <scene name='User:Marcin_Jozef_Suskiewicz/Sandbox_MarcinSuskiewicz/3/2'>>S-adenosyl-L-homocysteine</scene> and S-adenosyl-L-methionine to the enzyme. The ligand-binding cavity is predominately hydrophobic, but numerous polar interactions are likely to play a role in positioning the ligand in its specific orientation. There are <scene name='User:Marcin_Jozef_Suskiewicz/Sandbox_MarcinSuskiewicz/2/3'>11 polar interactions</scene> between NodS residues and S-adenosyl-L-methionine ligand and around 5-7 additional ones between the water molecules present in the binding pocket and the ligand. The <scene name='User:Marcin_Jozef_Suskiewicz/Sandbox_MarcinSuskiewicz/2/4'>amino group of the homocysteine amino acid moiety is anchored</scene> by the main-chain carbonyl groups of Gly 52 and Ala 114 from loop β1–αC and strand β4, respectively. The <scene name='User:Marcin_Jozef_Suskiewicz/Sandbox_MarcinSuskiewicz/2/5'>carboxy group of the same moiety interacts</scene> with the side chains of the basic amino acid residues Arg 31 and His 32 in helix αB. The <scene name='User:Marcin_Jozef_Suskiewicz/Sandbox_MarcinSuskiewicz/2/7'>hydroxyl groups of the ribose fragment of S-adenosyl-L-homocysteine form</scene> a pair of forked hydrogen bonds with both oxygen atoms of the carboxylic group of Asp 73 and a single hydrogen bond with main-chain nitrogen of Ala 54, Asp 73 being located at the tip of the β2 strand and Ala 54 in loop β1–αC. Finally, <scene name='User:Marcin_Jozef_Suskiewicz/Sandbox_MarcinSuskiewicz/2/8'>the adenine ring of the ligand is interacting</scene> with the main-chain nitrogen of Ile 99 and by the side chain of Asp 98, both from the β3–β4 loop. This adenine ring is also capable of making CH-π interactions with aliphatic side chains of valines 74 and 116. <scene name='User:Marcin_Jozef_Suskiewicz/Sandbox_MarcinSuskiewicz/2/9'>An additional interaction</scene> could potentially be formed between the sulfonium group of the ligand and the π system of Trp 20 when the methyl donor, S-adenosyl-L-methionine is bound instead of the homocysteine derivative. This interaction is likely to contribute to the larger affinity of NodS towards the methyl donor (a substrate) comparing to the homocysteine derivative (a products).	+	<scene name='User:Marcin_Jozef_Suskiewicz/Sandbox_MarcinSuskiewicz/3/1'>the structure of NodS bound to S-adenosyl-L-homocysteine</scene> gives reliable representation of the binding mode of both <scene name='User:Marcin_Jozef_Suskiewicz/Sandbox_MarcinSuskiewicz/3/2'>S-adenosyl-L-homocysteine</scene> and S-adenosyl-L-methionine to the enzyme. The ligand-binding cavity is predominately hydrophobic, but numerous polar interactions are likely to play a role in positioning the ligand in its specific orientation. There are <scene name='User:Marcin_Jozef_Suskiewicz/Sandbox_MarcinSuskiewicz/2/3'>11 polar interactions</scene> between NodS residues and S-adenosyl-L-methionine ligand and around 5-7 additional ones between the water molecules present in the binding pocket and the ligand. The <scene name='User:Marcin_Jozef_Suskiewicz/Sandbox_MarcinSuskiewicz/2/4'>amino group of the homocysteine amino acid moiety is anchored</scene> by the main-chain carbonyl groups of Gly 52 and Ala 114 from loop β1–αC and strand β4, respectively. The <scene name='User:Marcin_Jozef_Suskiewicz/Sandbox_MarcinSuskiewicz/2/5'>carboxy group of the same moiety interacts</scene> with the side chains of the basic amino acid residues Arg 31 and His 32 in helix αB. The <scene name='User:Marcin_Jozef_Suskiewicz/Sandbox_MarcinSuskiewicz/2/7'>hydroxyl groups of the ribose fragment of S-adenosyl-L-homocysteine form</scene> a pair of forked hydrogen bonds with both oxygen atoms of the carboxylic group of Asp 73 and a single hydrogen bond with main-chain nitrogen of Ala 54, Asp 73 being located at the tip of the β2 strand and Ala 54 in loop β1–αC. Finally, <scene name='User:Marcin_Jozef_Suskiewicz/Sandbox_MarcinSuskiewicz/2/8'>the adenine ring of the ligand is interacting</scene> with the main-chain nitrogen of Ile 99 and by the side chain of Asp 98, both from the β3–β4 loop. This adenine ring is also capable of making CH-π interactions with aliphatic side chains of valines 74 and 116. <scene name='User:Marcin_Jozef_Suskiewicz/Sandbox_MarcinSuskiewicz/2/9'>An additional interaction</scene> could potentially be formed between the sulfonium group of the ligand and the π system of Trp 20 when the methyl donor, S-adenosyl-L-methionine is bound instead of the homocysteine derivative. This interaction is likely to contribute to the larger affinity of NodS towards the methyl donor (a substrate) comparing to the homocysteine derivative (a products).

	</StructureSection>		</StructureSection>