1jhm
From Proteopedia
(New page: 200px<br /><applet load="1jhm" size="450" color="white" frame="true" align="right" spinBox="true" caption="1jhm, resolution 2.2Å" /> '''Three-dimensional Str...) |
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| - | [[Image:1jhm.jpg|left|200px]]<br /><applet load="1jhm" size=" | + | [[Image:1jhm.jpg|left|200px]]<br /><applet load="1jhm" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1jhm, resolution 2.2Å" /> | caption="1jhm, resolution 2.2Å" /> | ||
'''Three-dimensional Structure of CobT in Complex with 5-methylbenzimidazole'''<br /> | '''Three-dimensional Structure of CobT in Complex with 5-methylbenzimidazole'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Nicotinate mononucleotide (NaMN):5,6-dimethylbenzimidazole | + | Nicotinate mononucleotide (NaMN):5,6-dimethylbenzimidazole phosphoribosyltransferase (CobT) from Salmonella enterica plays a central role in the synthesis of alpha-ribazole, a key component of the lower ligand of cobalamin. Surprisingly, CobT can phosphoribosylate a wide range of aromatic substrates, giving rise to a wide variety of lower ligands in cobamides. To understand the molecular basis for this lack of substrate specificity, the x-ray structures of CobT complexed with adenine, 5-methylbenzimidazole, 5-methoxybenzimidazole, p-cresol, and phenol were determined. Furthermore, adenine, 5-methylbenzimidazole, 5-methoxybenzimidazole, and 2-hydroxypurine were observed to react with NaMN within the crystal lattice and undergo the phosphoribosyl transfer reaction to form product. Significantly, the stereochemistries of all products are identical to those found in vivo. Interestingly, p-cresol and phenol, which are the lower ligand in Sporomusa ovata, bound to CobT but did not react with NaMN. This study provides a structural explanation for how CobT can phosphoribosylate most of the commonly observed lower ligands found in cobamides with the exception of the phenolic lower ligands observed in S. ovata. This is accomplished with minor conformational changes in the side chains that constitute the 5,6-dimethylbenzimidazole binding site. These investigations are consistent with the implication that the nature of the lower ligand is controlled by metabolic factors rather by the specificity of the phosphoribosyltransferase. |
==About this Structure== | ==About this Structure== | ||
| - | 1JHM is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Salmonella_enterica Salmonella enterica] with PO4 and 5MB as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Nicotinate-nucleotide--dimethylbenzimidazole_phosphoribosyltransferase Nicotinate-nucleotide--dimethylbenzimidazole phosphoribosyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.4.2.21 2.4.2.21] Full crystallographic information is available from [http:// | + | 1JHM is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Salmonella_enterica Salmonella enterica] with <scene name='pdbligand=PO4:'>PO4</scene> and <scene name='pdbligand=5MB:'>5MB</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Nicotinate-nucleotide--dimethylbenzimidazole_phosphoribosyltransferase Nicotinate-nucleotide--dimethylbenzimidazole phosphoribosyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.4.2.21 2.4.2.21] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1JHM OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Salmonella enterica]] | [[Category: Salmonella enterica]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Cheong, C | + | [[Category: Cheong, C G.]] |
[[Category: Escalante-Semerena, J.]] | [[Category: Escalante-Semerena, J.]] | ||
[[Category: Rayment, I.]] | [[Category: Rayment, I.]] | ||
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[[Category: nn:dbi prt]] | [[Category: nn:dbi prt]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:22:43 2008'' |
Revision as of 11:22, 21 February 2008
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Three-dimensional Structure of CobT in Complex with 5-methylbenzimidazole
Overview
Nicotinate mononucleotide (NaMN):5,6-dimethylbenzimidazole phosphoribosyltransferase (CobT) from Salmonella enterica plays a central role in the synthesis of alpha-ribazole, a key component of the lower ligand of cobalamin. Surprisingly, CobT can phosphoribosylate a wide range of aromatic substrates, giving rise to a wide variety of lower ligands in cobamides. To understand the molecular basis for this lack of substrate specificity, the x-ray structures of CobT complexed with adenine, 5-methylbenzimidazole, 5-methoxybenzimidazole, p-cresol, and phenol were determined. Furthermore, adenine, 5-methylbenzimidazole, 5-methoxybenzimidazole, and 2-hydroxypurine were observed to react with NaMN within the crystal lattice and undergo the phosphoribosyl transfer reaction to form product. Significantly, the stereochemistries of all products are identical to those found in vivo. Interestingly, p-cresol and phenol, which are the lower ligand in Sporomusa ovata, bound to CobT but did not react with NaMN. This study provides a structural explanation for how CobT can phosphoribosylate most of the commonly observed lower ligands found in cobamides with the exception of the phenolic lower ligands observed in S. ovata. This is accomplished with minor conformational changes in the side chains that constitute the 5,6-dimethylbenzimidazole binding site. These investigations are consistent with the implication that the nature of the lower ligand is controlled by metabolic factors rather by the specificity of the phosphoribosyltransferase.
About this Structure
1JHM is a Single protein structure of sequence from Salmonella enterica with and as ligands. Active as Nicotinate-nucleotide--dimethylbenzimidazole phosphoribosyltransferase, with EC number 2.4.2.21 Full crystallographic information is available from OCA.
Reference
Structural investigation of the biosynthesis of alternative lower ligands for cobamides by nicotinate mononucleotide: 5,6-dimethylbenzimidazole phosphoribosyltransferase from Salmonella enterica., Cheong CG, Escalante-Semerena JC, Rayment I, J Biol Chem. 2001 Oct 5;276(40):37612-20. Epub 2001 Jul 5. PMID:11441022
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