User:Amer Ali/Sandbox 2 - Revision history

Amer Ali at 02:06, 4 May 2022

Amer Ali — Wed, 04 May 2022 02:06:10 GMT

←Older revision		Revision as of 02:06, 4 May 2022
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	Due to TrpS involvement in defense and biosynthesis of tryptophan for pathogenic bacteria, it is generally used a target for antibiotics. Overexpression studies found that tryptophan synthase is a biological target <ref name= "Abrahams"> DOI: 10.1038/s41598-017-09642-y </ref>. Examples of studied bacteria would be Streptococcus pneumoniae, Legionella pneumophila and Francisella tularensis. Research is done into the phylogenetic gaps these organisms have in order to better understand the unique features of TrpS orthologs for each bacteria <ref name= "Michalska"> PMID: 31316809 </ref>. One researched bacterium is the Mycobacterium tuberculosis (Mtb) in order to develop a drug that inhibits tryptophan synthase. The main reason is due to how widespread tuberculosis is (Mtb is a causative agent of tuberculosis). Drug research into Mtb is meant to find a way to combat the bacteria and limit its ability to develop resistance due to mutations, and strains are becoming resistant to TB therapy. In order to inhibit tryptophan synthase, sulfolanes and indoline-5-sulfonamides are used. More recent research related to tryptophan inhibition found that 3-amino-3-imino-2-phenyldiazenylpropanamide was a successful inhibitor by binding to the alpha subunit of TrpS. Other research involved in tryptophan synthase is the evolutionary origin of it and why it may have evolved. A study found that tryptophan synthase uses an atypical mechanism in order to achieve substrate specificity. Specifically, TrpS is capable of catalyzing a reaction with L-threonine (Thr), which creates [2S,3S]-beta-methyltryptophan. While Thr does bind efficiently, it decreases the affinity for indol and can disrupt allosteric signaling and regulation for the catalytic cycle. Thr is considered to be a universal and abundant metabolite, so research in seeing if TrpS can catalyze the synthesis of beta-MeTrp and seeing how TrpS can choose between Ser and Thr <ref name= "Buller"> PMID: 27935677 </ref>.		Due to TrpS involvement in defense and biosynthesis of tryptophan for pathogenic bacteria, it is generally used a target for antibiotics. Overexpression studies found that tryptophan synthase is a biological target <ref name= "Abrahams"> DOI: 10.1038/s41598-017-09642-y </ref>. Examples of studied bacteria would be Streptococcus pneumoniae, Legionella pneumophila and Francisella tularensis. Research is done into the phylogenetic gaps these organisms have in order to better understand the unique features of TrpS orthologs for each bacteria <ref name= "Michalska"> PMID: 31316809 </ref>. One researched bacterium is the Mycobacterium tuberculosis (Mtb) in order to develop a drug that inhibits tryptophan synthase. The main reason is due to how widespread tuberculosis is (Mtb is a causative agent of tuberculosis). Drug research into Mtb is meant to find a way to combat the bacteria and limit its ability to develop resistance due to mutations, and strains are becoming resistant to TB therapy. In order to inhibit tryptophan synthase, sulfolanes and indoline-5-sulfonamides are used. More recent research related to tryptophan inhibition found that 3-amino-3-imino-2-phenyldiazenylpropanamide was a successful inhibitor by binding to the alpha subunit of TrpS. Other research involved in tryptophan synthase is the evolutionary origin of it and why it may have evolved. A study found that tryptophan synthase uses an atypical mechanism in order to achieve substrate specificity. Specifically, TrpS is capable of catalyzing a reaction with L-threonine (Thr), which creates [2S,3S]-beta-methyltryptophan. While Thr does bind efficiently, it decreases the affinity for indol and can disrupt allosteric signaling and regulation for the catalytic cycle. Thr is considered to be a universal and abundant metabolite, so research in seeing if TrpS can catalyze the synthesis of beta-MeTrp and seeing how TrpS can choose between Ser and Thr <ref name= "Buller"> PMID: 27935677 </ref>.

-	~~[[Image:Tryptophan_synthasesteps.JPG]]~~	+
-	~~Tryptophan synthase reaction.<ref name= "Kriechbaumer"> DOI: 10.1186/1471-2229-8-44 </ref>~~	+

Amer Ali at 18:22, 2 May 2022

Amer Ali — Mon, 02 May 2022 18:22:38 GMT

←Older revision		Revision as of 18:22, 2 May 2022
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	Tryptophan synthase reaction.<ref name= "Kriechbaumer"> DOI: 10.1186/1471-2229-8-44 </ref>		Tryptophan synthase reaction.<ref name= "Kriechbaumer"> DOI: 10.1186/1471-2229-8-44 </ref>

-	== Structural highlights ==

-	This is a sample scene created with SAT to <scene name="/12/3456/Sample/1">color</scene> by Group, and another to make <scene name="/12/3456/Sample/2">a transparent representation</scene> of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes.

	</StructureSection>		</StructureSection>

Amer Ali at 18:22, 2 May 2022

Amer Ali — Mon, 02 May 2022 18:22:13 GMT

←Older revision		Revision as of 18:22, 2 May 2022
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	[[Image:Tryptophan_synthasesteps.JPG]]		[[Image:Tryptophan_synthasesteps.JPG]]
-	~~General scheme of the tryptophan~~ synthase reaction~~. Indole, which is formed from IGP by the α-subunits is channelled to β-subunits, which synthesize tryptophan from indole and serine~~.<ref name= "Kriechbaumer"> DOI: 10.1186/1471-2229-8-44 </ref>	+	Tryptophan synthase reaction.<ref name= "Kriechbaumer"> DOI: 10.1186/1471-2229-8-44 </ref>

	== Structural highlights ==		== Structural highlights ==

Amer Ali at 18:21, 2 May 2022

Amer Ali — Mon, 02 May 2022 18:21:04 GMT

←Older revision		Revision as of 18:21, 2 May 2022
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	[[Image:Tryptophan_synthasesteps.JPG]]		[[Image:Tryptophan_synthasesteps.JPG]]
-	General scheme of the tryptophan synthase reaction. Indole, which is formed from IGP by the α-subunits is channelled to β-subunits, which synthesize tryptophan from indole and serine.<ref name= "Kriechbaumer"> DOI: 10.1186/1471-2229-8-44 </ref	+	General scheme of the tryptophan synthase reaction. Indole, which is formed from IGP by the α-subunits is channelled to β-subunits, which synthesize tryptophan from indole and serine.<ref name= "Kriechbaumer"> DOI: 10.1186/1471-2229-8-44 </ref>

	== Structural highlights ==		== Structural highlights ==

Amer Ali at 18:20, 2 May 2022

Amer Ali — Mon, 02 May 2022 18:20:02 GMT

←Older revision		Revision as of 18:20, 2 May 2022
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	TrpS is a pyridoxal 5’-phosphate (PLP)-dependent enzyme. TrpS has an alpha and beta chain that form a linear alpha-beta-beta-alpha heterotetrameric complex <ref name= "Michalska"> PMID: 31316809 </ref>. This is termed as the alpha2beta2 complex, and each subunit is also referred to as TrpA and TrpB for the alpha and beta subunits respectively. The alpha active site contains catalytic residues Glu and Asp, and a hydrophobic intramolecular tunnel allows for the transport of indole from the alpha subunit active site to the beta subunit active site (Miles, 2001). The alpha and beta chain are encoded by trpA and trpB genes that are involved in TrpS regulatory operon. In bacteria and plants, the alpha and beta chains are separate, but in fungi the two chains are fused into one protein (Tryptophan synthase, alpha chain, active site). The alpha2beta2 tetramer complex contains pyridoxal-phosphate, glycerol-3-phosphate, Na+ ions. Another key site in tryptophan synthase is the monovalent cation (MVC) site, which is made up of cations like Na+ and K+, along with Cs+ <ref name= "Dierkers"> DOI: 10.1021/bi9008374</ref>. For regulation, TrpA and TrpB cycle between low-activity open conformation and a high-activity closed state. This is done by the binding of an IGP substrate to TrpA which promotes the high activity closed state which activates the TrpB high activity closed state. The states are reset back to low activity open conformation by the production of L-Trp external aldimine <ref name= "Michalska"> PMID: 31316809 </ref>.		TrpS is a pyridoxal 5’-phosphate (PLP)-dependent enzyme. TrpS has an alpha and beta chain that form a linear alpha-beta-beta-alpha heterotetrameric complex <ref name= "Michalska"> PMID: 31316809 </ref>. This is termed as the alpha2beta2 complex, and each subunit is also referred to as TrpA and TrpB for the alpha and beta subunits respectively. The alpha active site contains catalytic residues Glu and Asp, and a hydrophobic intramolecular tunnel allows for the transport of indole from the alpha subunit active site to the beta subunit active site (Miles, 2001). The alpha and beta chain are encoded by trpA and trpB genes that are involved in TrpS regulatory operon. In bacteria and plants, the alpha and beta chains are separate, but in fungi the two chains are fused into one protein (Tryptophan synthase, alpha chain, active site). The alpha2beta2 tetramer complex contains pyridoxal-phosphate, glycerol-3-phosphate, Na+ ions. Another key site in tryptophan synthase is the monovalent cation (MVC) site, which is made up of cations like Na+ and K+, along with Cs+ <ref name= "Dierkers"> DOI: 10.1021/bi9008374</ref>. For regulation, TrpA and TrpB cycle between low-activity open conformation and a high-activity closed state. This is done by the binding of an IGP substrate to TrpA which promotes the high activity closed state which activates the TrpB high activity closed state. The states are reset back to low activity open conformation by the production of L-Trp external aldimine <ref name= "Michalska"> PMID: 31316809 </ref>.

-	~~[Image:LabeledTRPS.JPG]]~~	+

Amer Ali at 18:19, 2 May 2022

Amer Ali — Mon, 02 May 2022 18:19:23 GMT

←Older revision		Revision as of 18:19, 2 May 2022
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	TrpS is a pyridoxal 5’-phosphate (PLP)-dependent enzyme. TrpS has an alpha and beta chain that form a linear alpha-beta-beta-alpha heterotetrameric complex <ref name= "Michalska"> PMID: 31316809 </ref>. This is termed as the alpha2beta2 complex, and each subunit is also referred to as TrpA and TrpB for the alpha and beta subunits respectively. The alpha active site contains catalytic residues Glu and Asp, and a hydrophobic intramolecular tunnel allows for the transport of indole from the alpha subunit active site to the beta subunit active site (Miles, 2001). The alpha and beta chain are encoded by trpA and trpB genes that are involved in TrpS regulatory operon. In bacteria and plants, the alpha and beta chains are separate, but in fungi the two chains are fused into one protein (Tryptophan synthase, alpha chain, active site). The alpha2beta2 tetramer complex contains pyridoxal-phosphate, glycerol-3-phosphate, Na+ ions. Another key site in tryptophan synthase is the monovalent cation (MVC) site, which is made up of cations like Na+ and K+, along with Cs+ <ref name= "Dierkers"> DOI: 10.1021/bi9008374</ref>. For regulation, TrpA and TrpB cycle between low-activity open conformation and a high-activity closed state. This is done by the binding of an IGP substrate to TrpA which promotes the high activity closed state which activates the TrpB high activity closed state. The states are reset back to low activity open conformation by the production of L-Trp external aldimine <ref name= "Michalska"> PMID: 31316809 </ref>.		TrpS is a pyridoxal 5’-phosphate (PLP)-dependent enzyme. TrpS has an alpha and beta chain that form a linear alpha-beta-beta-alpha heterotetrameric complex <ref name= "Michalska"> PMID: 31316809 </ref>. This is termed as the alpha2beta2 complex, and each subunit is also referred to as TrpA and TrpB for the alpha and beta subunits respectively. The alpha active site contains catalytic residues Glu and Asp, and a hydrophobic intramolecular tunnel allows for the transport of indole from the alpha subunit active site to the beta subunit active site (Miles, 2001). The alpha and beta chain are encoded by trpA and trpB genes that are involved in TrpS regulatory operon. In bacteria and plants, the alpha and beta chains are separate, but in fungi the two chains are fused into one protein (Tryptophan synthase, alpha chain, active site). The alpha2beta2 tetramer complex contains pyridoxal-phosphate, glycerol-3-phosphate, Na+ ions. Another key site in tryptophan synthase is the monovalent cation (MVC) site, which is made up of cations like Na+ and K+, along with Cs+ <ref name= "Dierkers"> DOI: 10.1021/bi9008374</ref>. For regulation, TrpA and TrpB cycle between low-activity open conformation and a high-activity closed state. This is done by the binding of an IGP substrate to TrpA which promotes the high activity closed state which activates the TrpB high activity closed state. The states are reset back to low activity open conformation by the production of L-Trp external aldimine <ref name= "Michalska"> PMID: 31316809 </ref>.

-	[[Image:LabeledTRPS.JPG]]	+	[Image:LabeledTRPS.JPG]]
-	~~Labeled structure of tryptophan synthase <ref name= "Loutchko"> DOI: 10.18452/19384 </ref>.~~	+

	== Function ==		== Function ==

Amer Ali at 03:14, 30 April 2022

Amer Ali — Sat, 30 Apr 2022 03:14:15 GMT

←Older revision		Revision as of 03:14, 30 April 2022
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	[[Image:LabeledTRPS.JPG]]		[[Image:LabeledTRPS.JPG]]
		+	Labeled structure of tryptophan synthase <ref name= "Loutchko"> DOI: 10.18452/19384 </ref>.

	== Function ==		== Function ==

Amer Ali at 03:11, 30 April 2022

Amer Ali — Sat, 30 Apr 2022 03:11:22 GMT

←Older revision		Revision as of 03:11, 30 April 2022
Line 8:		Line 8:
	TrpS is a pyridoxal 5’-phosphate (PLP)-dependent enzyme. TrpS has an alpha and beta chain that form a linear alpha-beta-beta-alpha heterotetrameric complex <ref name= "Michalska"> PMID: 31316809 </ref>. This is termed as the alpha2beta2 complex, and each subunit is also referred to as TrpA and TrpB for the alpha and beta subunits respectively. The alpha active site contains catalytic residues Glu and Asp, and a hydrophobic intramolecular tunnel allows for the transport of indole from the alpha subunit active site to the beta subunit active site (Miles, 2001). The alpha and beta chain are encoded by trpA and trpB genes that are involved in TrpS regulatory operon. In bacteria and plants, the alpha and beta chains are separate, but in fungi the two chains are fused into one protein (Tryptophan synthase, alpha chain, active site). The alpha2beta2 tetramer complex contains pyridoxal-phosphate, glycerol-3-phosphate, Na+ ions. Another key site in tryptophan synthase is the monovalent cation (MVC) site, which is made up of cations like Na+ and K+, along with Cs+ <ref name= "Dierkers"> DOI: 10.1021/bi9008374</ref>. For regulation, TrpA and TrpB cycle between low-activity open conformation and a high-activity closed state. This is done by the binding of an IGP substrate to TrpA which promotes the high activity closed state which activates the TrpB high activity closed state. The states are reset back to low activity open conformation by the production of L-Trp external aldimine <ref name= "Michalska"> PMID: 31316809 </ref>.		TrpS is a pyridoxal 5’-phosphate (PLP)-dependent enzyme. TrpS has an alpha and beta chain that form a linear alpha-beta-beta-alpha heterotetrameric complex <ref name= "Michalska"> PMID: 31316809 </ref>. This is termed as the alpha2beta2 complex, and each subunit is also referred to as TrpA and TrpB for the alpha and beta subunits respectively. The alpha active site contains catalytic residues Glu and Asp, and a hydrophobic intramolecular tunnel allows for the transport of indole from the alpha subunit active site to the beta subunit active site (Miles, 2001). The alpha and beta chain are encoded by trpA and trpB genes that are involved in TrpS regulatory operon. In bacteria and plants, the alpha and beta chains are separate, but in fungi the two chains are fused into one protein (Tryptophan synthase, alpha chain, active site). The alpha2beta2 tetramer complex contains pyridoxal-phosphate, glycerol-3-phosphate, Na+ ions. Another key site in tryptophan synthase is the monovalent cation (MVC) site, which is made up of cations like Na+ and K+, along with Cs+ <ref name= "Dierkers"> DOI: 10.1021/bi9008374</ref>. For regulation, TrpA and TrpB cycle between low-activity open conformation and a high-activity closed state. This is done by the binding of an IGP substrate to TrpA which promotes the high activity closed state which activates the TrpB high activity closed state. The states are reset back to low activity open conformation by the production of L-Trp external aldimine <ref name= "Michalska"> PMID: 31316809 </ref>.

		+	[[Image:LabeledTRPS.JPG]]

	== Function ==		== Function ==

Amer Ali at 03:08, 30 April 2022

Amer Ali — Sat, 30 Apr 2022 03:08:28 GMT

←Older revision		Revision as of 03:08, 30 April 2022
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	== Tryptophan Synthase ==		== Tryptophan Synthase ==
	<StructureSection load='1wbj' size='340' side='right' caption='Tryptophan synthase structure with alpha subunit (outer turqoise and light blue) and beta subunit (middle green and light green). Pyridoxal-phosphate, glycerol-3-phosphate, and Na+ ion shown within the structure (purple spheres). Red spheres represent H2O ' scene=''>		<StructureSection load='1wbj' size='340' side='right' caption='Tryptophan synthase structure with alpha subunit (outer turqoise and light blue) and beta subunit (middle green and light green). Pyridoxal-phosphate, glycerol-3-phosphate, and Na+ ion shown within the structure (purple spheres). Red spheres represent H2O ' scene=''>
-
-	<StructureSection load='2J9X' size='340' side='right' caption=' ' scene=''>

	== Introduction ==		== Introduction ==

Amer Ali at 03:07, 30 April 2022

Amer Ali — Sat, 30 Apr 2022 03:07:43 GMT

←Older revision		Revision as of 03:07, 30 April 2022
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	== Tryptophan Synthase ==		== Tryptophan Synthase ==
	<StructureSection load='1wbj' size='340' side='right' caption='Tryptophan synthase structure with alpha subunit (outer turqoise and light blue) and beta subunit (middle green and light green). Pyridoxal-phosphate, glycerol-3-phosphate, and Na+ ion shown within the structure (purple spheres). Red spheres represent H2O ' scene=''>		<StructureSection load='1wbj' size='340' side='right' caption='Tryptophan synthase structure with alpha subunit (outer turqoise and light blue) and beta subunit (middle green and light green). Pyridoxal-phosphate, glycerol-3-phosphate, and Na+ ion shown within the structure (purple spheres). Red spheres represent H2O ' scene=''>
		+
		+	<StructureSection load='2J9X' size='340' side='right' caption=' ' scene=''>

	== Introduction ==		== Introduction ==