Proteopedia - User contributions [en]

https://proteopedia.org/api.php?action=feedcontributions&feedformat=atom&user=Amer+Ali Proteopedia - User contributions [en] 2026-09-16T19:30:29Z User contributions MediaWiki 1.43.8 https://proteopedia.org/index.php?title=User:Amer_Ali/Sandbox_2&diff=3555496 User:Amer Ali/Sandbox 2 2022-05-04T02:06:10Z

<p>Amer Ali: </p> <hr /> <div>== Tryptophan Synthase ==<br /> <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=''><br /> <br /> == Introduction ==<br /> Tryptophan synthase (TrpS) is an enzyme mainly found in bacteria, plants, and fungi <ref name= "Kulik"> DOI: 10.1016/j.jmb.2005.07.014 </ref>. TrpS must be functional for pathogenic bacteria in macrophages to survive, and it is used as a way to avoid host immune response. Tryptophan is necessary for bacteria and lower eukaryotic organisms for protein synthesis. Salmonella typhimurium and Escherichia coli serve as model organisms for the understanding of TrpS processes and structure <ref name= "Kulik"> DOI: 10.1016/j.jmb.2005.07.014 </ref>.<br /> <br /> == Structure ==<br /> 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>.<br /> <br /> <br /> <br /> <br /> == Function ==<br /> TrpS main function is to catalyze the last two steps in tryptophan biosynthesis. Reactions take place at the active sites of the alpha and beta subunit. The alpha reaction, or TrpA, catalyzes the reaction involving indole-3-glycerol phosphate (IGP) cleavage, and the products made are indole and D-glyceraldehyde 3-phosphate. The alpha reaction is done through general acid-base catalysis <ref name= "Kulik"> DOI: 10.1016/j.jmb.2005.07.014 </ref>. The TrpA active site is located at the top of the central beta-barrel with two acidic residues, Glu and Asp, involved in the acid-base catalysis <ref name= "Michalska"> PMID: 31316809 </ref>. Indole will diffuse through the hydrophobic intramolecular tunnel that leads to the active site of the beta subunit. <br /> TrpB is a type II PLP-dependent enzyme with N- and C-terminal domains, and the TrpB active site is located in a cleft between these two domains that has the PLP cofactor <ref name= "Michalska"> PMID: 31316809 </ref>.The N-terminal is the communication domain which helps coordinate the activity in TrpA and TrpB active sites. beta reaction condenses the indole with the L-serine substrate to make L-tryptophan and water. The beta reaction is also called pyridoxal-5’-phosphate-dependent reaction <ref name= "Kulik"> DOI: 10.1016/j.jmb.2005.07.014 </ref>. The catalytic cycle is reversible until the C-C bond formation <ref name= "Buller"> PMID: 27935677 </ref>. The MVC site is involved in the catalysis and regulation of substrate channeling through the hydrophobic intramolecular tunnel. For in vitro, this site is involved in equilibrium distribution of the intermediates formed during the serine reaction. Tryptophan synthase is regulated by the propagation of allosteric signals via networds of noncovalent amino acid interactions. TrpS is regulated when the indole product from the alpha reaction is transferred to the beta reaction. A substitution of a surface netowork residue in the alpha reaction enhances TrpS production by controlling the opening of the indole channel and also stimulating the beta reaction <ref name= "D'Amico"> DOI: 10.3389/fmolb.2021.679915 </ref>. These regulations are necessary for the cell to efficiently use resources since tryptophan biosynthesis is an expensive process. <br /> <br /> == Relevance ==<br /> 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>.<br /> <br /> <br /> <br /> <br /> <br /> </StructureSection><br /> == References ==<br /> Miles E. W. (2001). Tryptophan synthase: a multienzyme complex with an intramolecular tunnel. Chemical record (New York, N.Y.), 1(2), 140–151. https://doi.org/10.1002/tcr.4<br /> <br /> <references/></div>

Amer Ali https://proteopedia.org/index.php?title=User:Amer_Ali/Sandbox_2&diff=3555195 User:Amer Ali/Sandbox 2 2022-05-02T18:22:38Z

<p>Amer Ali: </p> <hr /> <div>== Tryptophan Synthase ==<br /> <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=''><br /> <br /> == Introduction ==<br /> Tryptophan synthase (TrpS) is an enzyme mainly found in bacteria, plants, and fungi <ref name= "Kulik"> DOI: 10.1016/j.jmb.2005.07.014 </ref>. TrpS must be functional for pathogenic bacteria in macrophages to survive, and it is used as a way to avoid host immune response. Tryptophan is necessary for bacteria and lower eukaryotic organisms for protein synthesis. Salmonella typhimurium and Escherichia coli serve as model organisms for the understanding of TrpS processes and structure <ref name= "Kulik"> DOI: 10.1016/j.jmb.2005.07.014 </ref>.<br /> <br /> == Structure ==<br /> 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>.<br /> <br /> <br /> <br /> <br /> == Function ==<br /> TrpS main function is to catalyze the last two steps in tryptophan biosynthesis. Reactions take place at the active sites of the alpha and beta subunit. The alpha reaction, or TrpA, catalyzes the reaction involving indole-3-glycerol phosphate (IGP) cleavage, and the products made are indole and D-glyceraldehyde 3-phosphate. The alpha reaction is done through general acid-base catalysis <ref name= "Kulik"> DOI: 10.1016/j.jmb.2005.07.014 </ref>. The TrpA active site is located at the top of the central beta-barrel with two acidic residues, Glu and Asp, involved in the acid-base catalysis <ref name= "Michalska"> PMID: 31316809 </ref>. Indole will diffuse through the hydrophobic intramolecular tunnel that leads to the active site of the beta subunit. <br /> TrpB is a type II PLP-dependent enzyme with N- and C-terminal domains, and the TrpB active site is located in a cleft between these two domains that has the PLP cofactor <ref name= "Michalska"> PMID: 31316809 </ref>.The N-terminal is the communication domain which helps coordinate the activity in TrpA and TrpB active sites. beta reaction condenses the indole with the L-serine substrate to make L-tryptophan and water. The beta reaction is also called pyridoxal-5’-phosphate-dependent reaction <ref name= "Kulik"> DOI: 10.1016/j.jmb.2005.07.014 </ref>. The catalytic cycle is reversible until the C-C bond formation <ref name= "Buller"> PMID: 27935677 </ref>. The MVC site is involved in the catalysis and regulation of substrate channeling through the hydrophobic intramolecular tunnel. For in vitro, this site is involved in equilibrium distribution of the intermediates formed during the serine reaction. Tryptophan synthase is regulated by the propagation of allosteric signals via networds of noncovalent amino acid interactions. TrpS is regulated when the indole product from the alpha reaction is transferred to the beta reaction. A substitution of a surface netowork residue in the alpha reaction enhances TrpS production by controlling the opening of the indole channel and also stimulating the beta reaction <ref name= "D'Amico"> DOI: 10.3389/fmolb.2021.679915 </ref>. These regulations are necessary for the cell to efficiently use resources since tryptophan biosynthesis is an expensive process. <br /> <br /> == Relevance ==<br /> 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>.<br /> <br /> [[Image:Tryptophan_synthasesteps.JPG]]<br /> Tryptophan synthase reaction.<ref name= "Kriechbaumer"> DOI: 10.1186/1471-2229-8-44 </ref> <br /> <br /> <br /> <br /> </StructureSection><br /> == References ==<br /> Miles E. W. (2001). Tryptophan synthase: a multienzyme complex with an intramolecular tunnel. Chemical record (New York, N.Y.), 1(2), 140–151. https://doi.org/10.1002/tcr.4<br /> <br /> <references/></div>

Amer Ali https://proteopedia.org/index.php?title=User:Amer_Ali/Sandbox_2&diff=3555194 User:Amer Ali/Sandbox 2 2022-05-02T18:22:13Z

<p>Amer Ali: </p> <hr /> <div>== Tryptophan Synthase ==<br /> <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=''><br /> <br /> == Introduction ==<br /> Tryptophan synthase (TrpS) is an enzyme mainly found in bacteria, plants, and fungi <ref name= "Kulik"> DOI: 10.1016/j.jmb.2005.07.014 </ref>. TrpS must be functional for pathogenic bacteria in macrophages to survive, and it is used as a way to avoid host immune response. Tryptophan is necessary for bacteria and lower eukaryotic organisms for protein synthesis. Salmonella typhimurium and Escherichia coli serve as model organisms for the understanding of TrpS processes and structure <ref name= "Kulik"> DOI: 10.1016/j.jmb.2005.07.014 </ref>.<br /> <br /> == Structure ==<br /> 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>.<br /> <br /> <br /> <br /> <br /> == Function ==<br /> TrpS main function is to catalyze the last two steps in tryptophan biosynthesis. Reactions take place at the active sites of the alpha and beta subunit. The alpha reaction, or TrpA, catalyzes the reaction involving indole-3-glycerol phosphate (IGP) cleavage, and the products made are indole and D-glyceraldehyde 3-phosphate. The alpha reaction is done through general acid-base catalysis <ref name= "Kulik"> DOI: 10.1016/j.jmb.2005.07.014 </ref>. The TrpA active site is located at the top of the central beta-barrel with two acidic residues, Glu and Asp, involved in the acid-base catalysis <ref name= "Michalska"> PMID: 31316809 </ref>. Indole will diffuse through the hydrophobic intramolecular tunnel that leads to the active site of the beta subunit. <br /> TrpB is a type II PLP-dependent enzyme with N- and C-terminal domains, and the TrpB active site is located in a cleft between these two domains that has the PLP cofactor <ref name= "Michalska"> PMID: 31316809 </ref>.The N-terminal is the communication domain which helps coordinate the activity in TrpA and TrpB active sites. beta reaction condenses the indole with the L-serine substrate to make L-tryptophan and water. The beta reaction is also called pyridoxal-5’-phosphate-dependent reaction <ref name= "Kulik"> DOI: 10.1016/j.jmb.2005.07.014 </ref>. The catalytic cycle is reversible until the C-C bond formation <ref name= "Buller"> PMID: 27935677 </ref>. The MVC site is involved in the catalysis and regulation of substrate channeling through the hydrophobic intramolecular tunnel. For in vitro, this site is involved in equilibrium distribution of the intermediates formed during the serine reaction. Tryptophan synthase is regulated by the propagation of allosteric signals via networds of noncovalent amino acid interactions. TrpS is regulated when the indole product from the alpha reaction is transferred to the beta reaction. A substitution of a surface netowork residue in the alpha reaction enhances TrpS production by controlling the opening of the indole channel and also stimulating the beta reaction <ref name= "D'Amico"> DOI: 10.3389/fmolb.2021.679915 </ref>. These regulations are necessary for the cell to efficiently use resources since tryptophan biosynthesis is an expensive process. <br /> <br /> == Relevance ==<br /> 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>.<br /> <br /> [[Image:Tryptophan_synthasesteps.JPG]]<br /> Tryptophan synthase reaction.<ref name= "Kriechbaumer"> DOI: 10.1186/1471-2229-8-44 </ref> <br /> <br /> == Structural highlights ==<br /> <br /> 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.<br /> <br /> </StructureSection><br /> == References ==<br /> Miles E. W. (2001). Tryptophan synthase: a multienzyme complex with an intramolecular tunnel. Chemical record (New York, N.Y.), 1(2), 140–151. https://doi.org/10.1002/tcr.4<br /> <br /> <references/></div>

Amer Ali https://proteopedia.org/index.php?title=User:Amer_Ali/Sandbox_2&diff=3555193 User:Amer Ali/Sandbox 2 2022-05-02T18:21:04Z

<p>Amer Ali: </p> <hr /> <div>== Tryptophan Synthase ==<br /> <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=''><br /> <br /> == Introduction ==<br /> Tryptophan synthase (TrpS) is an enzyme mainly found in bacteria, plants, and fungi <ref name= "Kulik"> DOI: 10.1016/j.jmb.2005.07.014 </ref>. TrpS must be functional for pathogenic bacteria in macrophages to survive, and it is used as a way to avoid host immune response. Tryptophan is necessary for bacteria and lower eukaryotic organisms for protein synthesis. Salmonella typhimurium and Escherichia coli serve as model organisms for the understanding of TrpS processes and structure <ref name= "Kulik"> DOI: 10.1016/j.jmb.2005.07.014 </ref>.<br /> <br /> == Structure ==<br /> 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>.<br /> <br /> <br /> <br /> <br /> == Function ==<br /> TrpS main function is to catalyze the last two steps in tryptophan biosynthesis. Reactions take place at the active sites of the alpha and beta subunit. The alpha reaction, or TrpA, catalyzes the reaction involving indole-3-glycerol phosphate (IGP) cleavage, and the products made are indole and D-glyceraldehyde 3-phosphate. The alpha reaction is done through general acid-base catalysis <ref name= "Kulik"> DOI: 10.1016/j.jmb.2005.07.014 </ref>. The TrpA active site is located at the top of the central beta-barrel with two acidic residues, Glu and Asp, involved in the acid-base catalysis <ref name= "Michalska"> PMID: 31316809 </ref>. Indole will diffuse through the hydrophobic intramolecular tunnel that leads to the active site of the beta subunit. <br /> TrpB is a type II PLP-dependent enzyme with N- and C-terminal domains, and the TrpB active site is located in a cleft between these two domains that has the PLP cofactor <ref name= "Michalska"> PMID: 31316809 </ref>.The N-terminal is the communication domain which helps coordinate the activity in TrpA and TrpB active sites. beta reaction condenses the indole with the L-serine substrate to make L-tryptophan and water. The beta reaction is also called pyridoxal-5’-phosphate-dependent reaction <ref name= "Kulik"> DOI: 10.1016/j.jmb.2005.07.014 </ref>. The catalytic cycle is reversible until the C-C bond formation <ref name= "Buller"> PMID: 27935677 </ref>. The MVC site is involved in the catalysis and regulation of substrate channeling through the hydrophobic intramolecular tunnel. For in vitro, this site is involved in equilibrium distribution of the intermediates formed during the serine reaction. Tryptophan synthase is regulated by the propagation of allosteric signals via networds of noncovalent amino acid interactions. TrpS is regulated when the indole product from the alpha reaction is transferred to the beta reaction. A substitution of a surface netowork residue in the alpha reaction enhances TrpS production by controlling the opening of the indole channel and also stimulating the beta reaction <ref name= "D'Amico"> DOI: 10.3389/fmolb.2021.679915 </ref>. These regulations are necessary for the cell to efficiently use resources since tryptophan biosynthesis is an expensive process. <br /> <br /> == Relevance ==<br /> 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>.<br /> <br /> [[Image:Tryptophan_synthasesteps.JPG]]<br /> 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> <br /> <br /> == Structural highlights ==<br /> <br /> 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.<br /> <br /> </StructureSection><br /> == References ==<br /> Miles E. W. (2001). Tryptophan synthase: a multienzyme complex with an intramolecular tunnel. Chemical record (New York, N.Y.), 1(2), 140–151. https://doi.org/10.1002/tcr.4<br /> <br /> <references/></div>

Amer Ali https://proteopedia.org/index.php?title=User:Amer_Ali/Sandbox_2&diff=3555192 User:Amer Ali/Sandbox 2 2022-05-02T18:20:02Z

<p>Amer Ali: </p> <hr /> <div>== Tryptophan Synthase ==<br /> <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=''><br /> <br /> == Introduction ==<br /> Tryptophan synthase (TrpS) is an enzyme mainly found in bacteria, plants, and fungi <ref name= "Kulik"> DOI: 10.1016/j.jmb.2005.07.014 </ref>. TrpS must be functional for pathogenic bacteria in macrophages to survive, and it is used as a way to avoid host immune response. Tryptophan is necessary for bacteria and lower eukaryotic organisms for protein synthesis. Salmonella typhimurium and Escherichia coli serve as model organisms for the understanding of TrpS processes and structure <ref name= "Kulik"> DOI: 10.1016/j.jmb.2005.07.014 </ref>.<br /> <br /> == Structure ==<br /> 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>.<br /> <br /> <br /> <br /> <br /> == Function ==<br /> TrpS main function is to catalyze the last two steps in tryptophan biosynthesis. Reactions take place at the active sites of the alpha and beta subunit. The alpha reaction, or TrpA, catalyzes the reaction involving indole-3-glycerol phosphate (IGP) cleavage, and the products made are indole and D-glyceraldehyde 3-phosphate. The alpha reaction is done through general acid-base catalysis <ref name= "Kulik"> DOI: 10.1016/j.jmb.2005.07.014 </ref>. The TrpA active site is located at the top of the central beta-barrel with two acidic residues, Glu and Asp, involved in the acid-base catalysis <ref name= "Michalska"> PMID: 31316809 </ref>. Indole will diffuse through the hydrophobic intramolecular tunnel that leads to the active site of the beta subunit. <br /> TrpB is a type II PLP-dependent enzyme with N- and C-terminal domains, and the TrpB active site is located in a cleft between these two domains that has the PLP cofactor <ref name= "Michalska"> PMID: 31316809 </ref>.The N-terminal is the communication domain which helps coordinate the activity in TrpA and TrpB active sites. beta reaction condenses the indole with the L-serine substrate to make L-tryptophan and water. The beta reaction is also called pyridoxal-5’-phosphate-dependent reaction <ref name= "Kulik"> DOI: 10.1016/j.jmb.2005.07.014 </ref>. The catalytic cycle is reversible until the C-C bond formation <ref name= "Buller"> PMID: 27935677 </ref>. The MVC site is involved in the catalysis and regulation of substrate channeling through the hydrophobic intramolecular tunnel. For in vitro, this site is involved in equilibrium distribution of the intermediates formed during the serine reaction. Tryptophan synthase is regulated by the propagation of allosteric signals via networds of noncovalent amino acid interactions. TrpS is regulated when the indole product from the alpha reaction is transferred to the beta reaction. A substitution of a surface netowork residue in the alpha reaction enhances TrpS production by controlling the opening of the indole channel and also stimulating the beta reaction <ref name= "D'Amico"> DOI: 10.3389/fmolb.2021.679915 </ref>. These regulations are necessary for the cell to efficiently use resources since tryptophan biosynthesis is an expensive process. <br /> <br /> == Relevance ==<br /> 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>.<br /> <br /> [[Image:Tryptophan_synthasesteps.JPG]]<br /> 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 <br /> <br /> == Structural highlights ==<br /> <br /> 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.<br /> <br /> </StructureSection><br /> == References ==<br /> Miles E. W. (2001). Tryptophan synthase: a multienzyme complex with an intramolecular tunnel. Chemical record (New York, N.Y.), 1(2), 140–151. https://doi.org/10.1002/tcr.4<br /> <br /> <references/></div>

Amer Ali https://proteopedia.org/index.php?title=User:Amer_Ali/Sandbox_2&diff=3555191 User:Amer Ali/Sandbox 2 2022-05-02T18:19:23Z

<p>Amer Ali: </p> <hr /> <div>== Tryptophan Synthase ==<br /> <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=''><br /> <br /> == Introduction ==<br /> Tryptophan synthase (TrpS) is an enzyme mainly found in bacteria, plants, and fungi <ref name= "Kulik"> DOI: 10.1016/j.jmb.2005.07.014 </ref>. TrpS must be functional for pathogenic bacteria in macrophages to survive, and it is used as a way to avoid host immune response. Tryptophan is necessary for bacteria and lower eukaryotic organisms for protein synthesis. Salmonella typhimurium and Escherichia coli serve as model organisms for the understanding of TrpS processes and structure <ref name= "Kulik"> DOI: 10.1016/j.jmb.2005.07.014 </ref>.<br /> <br /> == Structure ==<br /> 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>.<br /> <br /> [Image:LabeledTRPS.JPG]]<br /> <br /> <br /> == Function ==<br /> TrpS main function is to catalyze the last two steps in tryptophan biosynthesis. Reactions take place at the active sites of the alpha and beta subunit. The alpha reaction, or TrpA, catalyzes the reaction involving indole-3-glycerol phosphate (IGP) cleavage, and the products made are indole and D-glyceraldehyde 3-phosphate. The alpha reaction is done through general acid-base catalysis <ref name= "Kulik"> DOI: 10.1016/j.jmb.2005.07.014 </ref>. The TrpA active site is located at the top of the central beta-barrel with two acidic residues, Glu and Asp, involved in the acid-base catalysis <ref name= "Michalska"> PMID: 31316809 </ref>. Indole will diffuse through the hydrophobic intramolecular tunnel that leads to the active site of the beta subunit. <br /> TrpB is a type II PLP-dependent enzyme with N- and C-terminal domains, and the TrpB active site is located in a cleft between these two domains that has the PLP cofactor <ref name= "Michalska"> PMID: 31316809 </ref>.The N-terminal is the communication domain which helps coordinate the activity in TrpA and TrpB active sites. beta reaction condenses the indole with the L-serine substrate to make L-tryptophan and water. The beta reaction is also called pyridoxal-5’-phosphate-dependent reaction <ref name= "Kulik"> DOI: 10.1016/j.jmb.2005.07.014 </ref>. The catalytic cycle is reversible until the C-C bond formation <ref name= "Buller"> PMID: 27935677 </ref>. The MVC site is involved in the catalysis and regulation of substrate channeling through the hydrophobic intramolecular tunnel. For in vitro, this site is involved in equilibrium distribution of the intermediates formed during the serine reaction. Tryptophan synthase is regulated by the propagation of allosteric signals via networds of noncovalent amino acid interactions. TrpS is regulated when the indole product from the alpha reaction is transferred to the beta reaction. A substitution of a surface netowork residue in the alpha reaction enhances TrpS production by controlling the opening of the indole channel and also stimulating the beta reaction <ref name= "D'Amico"> DOI: 10.3389/fmolb.2021.679915 </ref>. These regulations are necessary for the cell to efficiently use resources since tryptophan biosynthesis is an expensive process. <br /> <br /> == Relevance ==<br /> 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>.<br /> <br /> [[Image:Tryptophan_synthasesteps.JPG]]<br /> 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 <br /> <br /> == Structural highlights ==<br /> <br /> 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.<br /> <br /> </StructureSection><br /> == References ==<br /> Miles E. W. (2001). Tryptophan synthase: a multienzyme complex with an intramolecular tunnel. Chemical record (New York, N.Y.), 1(2), 140–151. https://doi.org/10.1002/tcr.4<br /> <br /> <references/></div>

Amer Ali https://proteopedia.org/index.php?title=User:Amer_Ali/Sandbox_2&diff=3554527 User:Amer Ali/Sandbox 2 2022-04-30T03:14:15Z

<p>Amer Ali: </p> <hr /> <div>== Tryptophan Synthase ==<br /> <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=''><br /> <br /> == Introduction ==<br /> Tryptophan synthase (TrpS) is an enzyme mainly found in bacteria, plants, and fungi <ref name= "Kulik"> DOI: 10.1016/j.jmb.2005.07.014 </ref>. TrpS must be functional for pathogenic bacteria in macrophages to survive, and it is used as a way to avoid host immune response. Tryptophan is necessary for bacteria and lower eukaryotic organisms for protein synthesis. Salmonella typhimurium and Escherichia coli serve as model organisms for the understanding of TrpS processes and structure <ref name= "Kulik"> DOI: 10.1016/j.jmb.2005.07.014 </ref>.<br /> <br /> == Structure ==<br /> 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>.<br /> <br /> [[Image:LabeledTRPS.JPG]]<br /> Labeled structure of tryptophan synthase <ref name= "Loutchko"> DOI: 10.18452/19384 </ref>.<br /> <br /> == Function ==<br /> TrpS main function is to catalyze the last two steps in tryptophan biosynthesis. Reactions take place at the active sites of the alpha and beta subunit. The alpha reaction, or TrpA, catalyzes the reaction involving indole-3-glycerol phosphate (IGP) cleavage, and the products made are indole and D-glyceraldehyde 3-phosphate. The alpha reaction is done through general acid-base catalysis <ref name= "Kulik"> DOI: 10.1016/j.jmb.2005.07.014 </ref>. The TrpA active site is located at the top of the central beta-barrel with two acidic residues, Glu and Asp, involved in the acid-base catalysis <ref name= "Michalska"> PMID: 31316809 </ref>. Indole will diffuse through the hydrophobic intramolecular tunnel that leads to the active site of the beta subunit. <br /> TrpB is a type II PLP-dependent enzyme with N- and C-terminal domains, and the TrpB active site is located in a cleft between these two domains that has the PLP cofactor <ref name= "Michalska"> PMID: 31316809 </ref>.The N-terminal is the communication domain which helps coordinate the activity in TrpA and TrpB active sites. beta reaction condenses the indole with the L-serine substrate to make L-tryptophan and water. The beta reaction is also called pyridoxal-5’-phosphate-dependent reaction <ref name= "Kulik"> DOI: 10.1016/j.jmb.2005.07.014 </ref>. The catalytic cycle is reversible until the C-C bond formation <ref name= "Buller"> PMID: 27935677 </ref>. The MVC site is involved in the catalysis and regulation of substrate channeling through the hydrophobic intramolecular tunnel. For in vitro, this site is involved in equilibrium distribution of the intermediates formed during the serine reaction. Tryptophan synthase is regulated by the propagation of allosteric signals via networds of noncovalent amino acid interactions. TrpS is regulated when the indole product from the alpha reaction is transferred to the beta reaction. A substitution of a surface netowork residue in the alpha reaction enhances TrpS production by controlling the opening of the indole channel and also stimulating the beta reaction <ref name= "D'Amico"> DOI: 10.3389/fmolb.2021.679915 </ref>. These regulations are necessary for the cell to efficiently use resources since tryptophan biosynthesis is an expensive process. <br /> <br /> == Relevance ==<br /> 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>.<br /> <br /> [[Image:Tryptophan_synthasesteps.JPG]]<br /> 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 <br /> <br /> == Structural highlights ==<br /> <br /> 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.<br /> <br /> </StructureSection><br /> == References ==<br /> Miles E. W. (2001). Tryptophan synthase: a multienzyme complex with an intramolecular tunnel. Chemical record (New York, N.Y.), 1(2), 140–151. https://doi.org/10.1002/tcr.4<br /> <br /> <references/></div>

Amer Ali https://proteopedia.org/index.php?title=User:Amer_Ali/Sandbox_2&diff=3554526 User:Amer Ali/Sandbox 2 2022-04-30T03:11:22Z

<p>Amer Ali: </p> <hr /> <div>== Tryptophan Synthase ==<br /> <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=''><br /> <br /> == Introduction ==<br /> Tryptophan synthase (TrpS) is an enzyme mainly found in bacteria, plants, and fungi <ref name= "Kulik"> DOI: 10.1016/j.jmb.2005.07.014 </ref>. TrpS must be functional for pathogenic bacteria in macrophages to survive, and it is used as a way to avoid host immune response. Tryptophan is necessary for bacteria and lower eukaryotic organisms for protein synthesis. Salmonella typhimurium and Escherichia coli serve as model organisms for the understanding of TrpS processes and structure <ref name= "Kulik"> DOI: 10.1016/j.jmb.2005.07.014 </ref>.<br /> <br /> == Structure ==<br /> 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>.<br /> <br /> [[Image:LabeledTRPS.JPG]]<br /> <br /> == Function ==<br /> TrpS main function is to catalyze the last two steps in tryptophan biosynthesis. Reactions take place at the active sites of the alpha and beta subunit. The alpha reaction, or TrpA, catalyzes the reaction involving indole-3-glycerol phosphate (IGP) cleavage, and the products made are indole and D-glyceraldehyde 3-phosphate. The alpha reaction is done through general acid-base catalysis <ref name= "Kulik"> DOI: 10.1016/j.jmb.2005.07.014 </ref>. The TrpA active site is located at the top of the central beta-barrel with two acidic residues, Glu and Asp, involved in the acid-base catalysis <ref name= "Michalska"> PMID: 31316809 </ref>. Indole will diffuse through the hydrophobic intramolecular tunnel that leads to the active site of the beta subunit. <br /> TrpB is a type II PLP-dependent enzyme with N- and C-terminal domains, and the TrpB active site is located in a cleft between these two domains that has the PLP cofactor <ref name= "Michalska"> PMID: 31316809 </ref>.The N-terminal is the communication domain which helps coordinate the activity in TrpA and TrpB active sites. beta reaction condenses the indole with the L-serine substrate to make L-tryptophan and water. The beta reaction is also called pyridoxal-5’-phosphate-dependent reaction <ref name= "Kulik"> DOI: 10.1016/j.jmb.2005.07.014 </ref>. The catalytic cycle is reversible until the C-C bond formation <ref name= "Buller"> PMID: 27935677 </ref>. The MVC site is involved in the catalysis and regulation of substrate channeling through the hydrophobic intramolecular tunnel. For in vitro, this site is involved in equilibrium distribution of the intermediates formed during the serine reaction. Tryptophan synthase is regulated by the propagation of allosteric signals via networds of noncovalent amino acid interactions. TrpS is regulated when the indole product from the alpha reaction is transferred to the beta reaction. A substitution of a surface netowork residue in the alpha reaction enhances TrpS production by controlling the opening of the indole channel and also stimulating the beta reaction <ref name= "D'Amico"> DOI: 10.3389/fmolb.2021.679915 </ref>. These regulations are necessary for the cell to efficiently use resources since tryptophan biosynthesis is an expensive process. <br /> <br /> == Relevance ==<br /> 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>.<br /> <br /> [[Image:Tryptophan_synthasesteps.JPG]]<br /> 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 <br /> <br /> == Structural highlights ==<br /> <br /> 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.<br /> <br /> </StructureSection><br /> == References ==<br /> Miles E. W. (2001). Tryptophan synthase: a multienzyme complex with an intramolecular tunnel. Chemical record (New York, N.Y.), 1(2), 140–151. https://doi.org/10.1002/tcr.4<br /> <br /> <references/></div>

Amer Ali https://proteopedia.org/index.php?title=File:LabeledTRPS.JPG&diff=3554525 File:LabeledTRPS.JPG 2022-04-30T03:09:13Z

<p>Amer Ali: Labeled tryptophan synthase</p> <hr /> <div>== Summary ==<br /> Labeled tryptophan synthase<br /> == Licensing ==<br /> {{subst:No license from license selector|Somewebsite}}</div>

Amer Ali https://proteopedia.org/index.php?title=User:Amer_Ali/Sandbox_2&diff=3554524 User:Amer Ali/Sandbox 2 2022-04-30T03:08:28Z

<p>Amer Ali: </p> <hr /> <div>== Tryptophan Synthase ==<br /> <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=''><br /> <br /> == Introduction ==<br /> Tryptophan synthase (TrpS) is an enzyme mainly found in bacteria, plants, and fungi <ref name= "Kulik"> DOI: 10.1016/j.jmb.2005.07.014 </ref>. TrpS must be functional for pathogenic bacteria in macrophages to survive, and it is used as a way to avoid host immune response. Tryptophan is necessary for bacteria and lower eukaryotic organisms for protein synthesis. Salmonella typhimurium and Escherichia coli serve as model organisms for the understanding of TrpS processes and structure <ref name= "Kulik"> DOI: 10.1016/j.jmb.2005.07.014 </ref>.<br /> <br /> == Structure ==<br /> 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>.<br /> <br /> <br /> == Function ==<br /> TrpS main function is to catalyze the last two steps in tryptophan biosynthesis. Reactions take place at the active sites of the alpha and beta subunit. The alpha reaction, or TrpA, catalyzes the reaction involving indole-3-glycerol phosphate (IGP) cleavage, and the products made are indole and D-glyceraldehyde 3-phosphate. The alpha reaction is done through general acid-base catalysis <ref name= "Kulik"> DOI: 10.1016/j.jmb.2005.07.014 </ref>. The TrpA active site is located at the top of the central beta-barrel with two acidic residues, Glu and Asp, involved in the acid-base catalysis <ref name= "Michalska"> PMID: 31316809 </ref>. Indole will diffuse through the hydrophobic intramolecular tunnel that leads to the active site of the beta subunit. <br /> TrpB is a type II PLP-dependent enzyme with N- and C-terminal domains, and the TrpB active site is located in a cleft between these two domains that has the PLP cofactor <ref name= "Michalska"> PMID: 31316809 </ref>.The N-terminal is the communication domain which helps coordinate the activity in TrpA and TrpB active sites. beta reaction condenses the indole with the L-serine substrate to make L-tryptophan and water. The beta reaction is also called pyridoxal-5’-phosphate-dependent reaction <ref name= "Kulik"> DOI: 10.1016/j.jmb.2005.07.014 </ref>. The catalytic cycle is reversible until the C-C bond formation <ref name= "Buller"> PMID: 27935677 </ref>. The MVC site is involved in the catalysis and regulation of substrate channeling through the hydrophobic intramolecular tunnel. For in vitro, this site is involved in equilibrium distribution of the intermediates formed during the serine reaction. Tryptophan synthase is regulated by the propagation of allosteric signals via networds of noncovalent amino acid interactions. TrpS is regulated when the indole product from the alpha reaction is transferred to the beta reaction. A substitution of a surface netowork residue in the alpha reaction enhances TrpS production by controlling the opening of the indole channel and also stimulating the beta reaction <ref name= "D'Amico"> DOI: 10.3389/fmolb.2021.679915 </ref>. These regulations are necessary for the cell to efficiently use resources since tryptophan biosynthesis is an expensive process. <br /> <br /> == Relevance ==<br /> 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>.<br /> <br /> [[Image:Tryptophan_synthasesteps.JPG]]<br /> 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 <br /> <br /> == Structural highlights ==<br /> <br /> 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.<br /> <br /> </StructureSection><br /> == References ==<br /> Miles E. W. (2001). Tryptophan synthase: a multienzyme complex with an intramolecular tunnel. Chemical record (New York, N.Y.), 1(2), 140–151. https://doi.org/10.1002/tcr.4<br /> <br /> <references/></div>

Amer Ali https://proteopedia.org/index.php?title=User:Amer_Ali/Sandbox_2&diff=3554523 User:Amer Ali/Sandbox 2 2022-04-30T03:07:43Z

<p>Amer Ali: </p> <hr /> <div>== Tryptophan Synthase ==<br /> <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=''><br /> <br /> <StructureSection load='2J9X' size='340' side='right' caption=' ' scene=''><br /> <br /> == Introduction ==<br /> Tryptophan synthase (TrpS) is an enzyme mainly found in bacteria, plants, and fungi <ref name= "Kulik"> DOI: 10.1016/j.jmb.2005.07.014 </ref>. TrpS must be functional for pathogenic bacteria in macrophages to survive, and it is used as a way to avoid host immune response. Tryptophan is necessary for bacteria and lower eukaryotic organisms for protein synthesis. Salmonella typhimurium and Escherichia coli serve as model organisms for the understanding of TrpS processes and structure <ref name= "Kulik"> DOI: 10.1016/j.jmb.2005.07.014 </ref>.<br /> <br /> == Structure ==<br /> 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>.<br /> <br /> <br /> == Function ==<br /> TrpS main function is to catalyze the last two steps in tryptophan biosynthesis. Reactions take place at the active sites of the alpha and beta subunit. The alpha reaction, or TrpA, catalyzes the reaction involving indole-3-glycerol phosphate (IGP) cleavage, and the products made are indole and D-glyceraldehyde 3-phosphate. The alpha reaction is done through general acid-base catalysis <ref name= "Kulik"> DOI: 10.1016/j.jmb.2005.07.014 </ref>. The TrpA active site is located at the top of the central beta-barrel with two acidic residues, Glu and Asp, involved in the acid-base catalysis <ref name= "Michalska"> PMID: 31316809 </ref>. Indole will diffuse through the hydrophobic intramolecular tunnel that leads to the active site of the beta subunit. <br /> TrpB is a type II PLP-dependent enzyme with N- and C-terminal domains, and the TrpB active site is located in a cleft between these two domains that has the PLP cofactor <ref name= "Michalska"> PMID: 31316809 </ref>.The N-terminal is the communication domain which helps coordinate the activity in TrpA and TrpB active sites. beta reaction condenses the indole with the L-serine substrate to make L-tryptophan and water. The beta reaction is also called pyridoxal-5’-phosphate-dependent reaction <ref name= "Kulik"> DOI: 10.1016/j.jmb.2005.07.014 </ref>. The catalytic cycle is reversible until the C-C bond formation <ref name= "Buller"> PMID: 27935677 </ref>. The MVC site is involved in the catalysis and regulation of substrate channeling through the hydrophobic intramolecular tunnel. For in vitro, this site is involved in equilibrium distribution of the intermediates formed during the serine reaction. Tryptophan synthase is regulated by the propagation of allosteric signals via networds of noncovalent amino acid interactions. TrpS is regulated when the indole product from the alpha reaction is transferred to the beta reaction. A substitution of a surface netowork residue in the alpha reaction enhances TrpS production by controlling the opening of the indole channel and also stimulating the beta reaction <ref name= "D'Amico"> DOI: 10.3389/fmolb.2021.679915 </ref>. These regulations are necessary for the cell to efficiently use resources since tryptophan biosynthesis is an expensive process. <br /> <br /> == Relevance ==<br /> 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>.<br /> <br /> [[Image:Tryptophan_synthasesteps.JPG]]<br /> 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 <br /> <br /> == Structural highlights ==<br /> <br /> 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.<br /> <br /> </StructureSection><br /> == References ==<br /> Miles E. W. (2001). Tryptophan synthase: a multienzyme complex with an intramolecular tunnel. Chemical record (New York, N.Y.), 1(2), 140–151. https://doi.org/10.1002/tcr.4<br /> <br /> <references/></div>

Amer Ali https://proteopedia.org/index.php?title=User:Amer_Ali/Sandbox_2&diff=3554522 User:Amer Ali/Sandbox 2 2022-04-30T02:51:10Z

<p>Amer Ali: </p> <hr /> <div>== Tryptophan Synthase ==<br /> <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=''><br /> <br /> == Introduction ==<br /> Tryptophan synthase (TrpS) is an enzyme mainly found in bacteria, plants, and fungi <ref name= "Kulik"> DOI: 10.1016/j.jmb.2005.07.014 </ref>. TrpS must be functional for pathogenic bacteria in macrophages to survive, and it is used as a way to avoid host immune response. Tryptophan is necessary for bacteria and lower eukaryotic organisms for protein synthesis. Salmonella typhimurium and Escherichia coli serve as model organisms for the understanding of TrpS processes and structure <ref name= "Kulik"> DOI: 10.1016/j.jmb.2005.07.014 </ref>.<br /> <br /> == Structure ==<br /> 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>.<br /> <br /> <br /> == Function ==<br /> TrpS main function is to catalyze the last two steps in tryptophan biosynthesis. Reactions take place at the active sites of the alpha and beta subunit. The alpha reaction, or TrpA, catalyzes the reaction involving indole-3-glycerol phosphate (IGP) cleavage, and the products made are indole and D-glyceraldehyde 3-phosphate. The alpha reaction is done through general acid-base catalysis <ref name= "Kulik"> DOI: 10.1016/j.jmb.2005.07.014 </ref>. The TrpA active site is located at the top of the central beta-barrel with two acidic residues, Glu and Asp, involved in the acid-base catalysis <ref name= "Michalska"> PMID: 31316809 </ref>. Indole will diffuse through the hydrophobic intramolecular tunnel that leads to the active site of the beta subunit. <br /> TrpB is a type II PLP-dependent enzyme with N- and C-terminal domains, and the TrpB active site is located in a cleft between these two domains that has the PLP cofactor <ref name= "Michalska"> PMID: 31316809 </ref>.The N-terminal is the communication domain which helps coordinate the activity in TrpA and TrpB active sites. beta reaction condenses the indole with the L-serine substrate to make L-tryptophan and water. The beta reaction is also called pyridoxal-5’-phosphate-dependent reaction <ref name= "Kulik"> DOI: 10.1016/j.jmb.2005.07.014 </ref>. The catalytic cycle is reversible until the C-C bond formation <ref name= "Buller"> PMID: 27935677 </ref>. The MVC site is involved in the catalysis and regulation of substrate channeling through the hydrophobic intramolecular tunnel. For in vitro, this site is involved in equilibrium distribution of the intermediates formed during the serine reaction. Tryptophan synthase is regulated by the propagation of allosteric signals via networds of noncovalent amino acid interactions. TrpS is regulated when the indole product from the alpha reaction is transferred to the beta reaction. A substitution of a surface netowork residue in the alpha reaction enhances TrpS production by controlling the opening of the indole channel and also stimulating the beta reaction <ref name= "D'Amico"> DOI: 10.3389/fmolb.2021.679915 </ref>. These regulations are necessary for the cell to efficiently use resources since tryptophan biosynthesis is an expensive process. <br /> <br /> == Relevance ==<br /> 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>.<br /> <br /> [[Image:Tryptophan_synthasesteps.JPG]]<br /> 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 <br /> <br /> == Structural highlights ==<br /> <br /> 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.<br /> <br /> </StructureSection><br /> == References ==<br /> Miles E. W. (2001). Tryptophan synthase: a multienzyme complex with an intramolecular tunnel. Chemical record (New York, N.Y.), 1(2), 140–151. https://doi.org/10.1002/tcr.4<br /> <br /> <references/></div>

Amer Ali https://proteopedia.org/index.php?title=User:Amer_Ali/Sandbox_2&diff=3554519 User:Amer Ali/Sandbox 2 2022-04-30T02:38:05Z

<p>Amer Ali: </p> <hr /> <div>== Tryptophan Synthase ==<br /> <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=''><br /> <br /> == Introduction ==<br /> Tryptophan synthase (TrpS) is an enzyme mainly found in bacteria, plants, and fungi <ref name= "Kulik"> DOI: 10.1016/j.jmb.2005.07.014 </ref>. TrpS must be functional for pathogenic bacteria in macrophages to survive, and it is used as a way to avoid host immune response. Tryptophan is necessary for bacteria and lower eukaryotic organisms for protein synthesis. Salmonella typhimurium and Escherichia coli serve as model organisms for the understanding of TrpS processes and structure <ref name= "Kulik"> DOI: 10.1016/j.jmb.2005.07.014 </ref>.<br /> <br /> == Structure ==<br /> 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>.<br /> <br /> <br /> == Function ==<br /> TrpS main function is to catalyze the last two steps in tryptophan biosynthesis. Reactions take place at the active sites of the alpha and beta subunit. The alpha reaction, or TrpA, catalyzes the reaction involving indole-3-glycerol phosphate (IGP) cleavage, and the products made are indole and D-glyceraldehyde 3-phosphate. The alpha reaction is done through general acid-base catalysis <ref name= "Kulik"> DOI: 10.1016/j.jmb.2005.07.014 </ref>. The TrpA active site is located at the top of the central beta-barrel with two acidic residues, Glu and Asp, involved in the acid-base catalysis <ref name= "Michalska"> PMID: 31316809 </ref>. Indole will diffuse through the hydrophobic intramolecular tunnel that leads to the active site of the beta subunit. <br /> TrpB is a type II PLP-dependent enzyme with N- and C-terminal domains, and the TrpB active site is located in a cleft between these two domains that has the PLP cofactor <ref name= "Michalska"> PMID: 31316809 </ref>.The N-terminal is the communication domain which helps coordinate the activity in TrpA and TrpB active sites. beta reaction condenses the indole with the L-serine substrate to make L-tryptophan and water. The beta reaction is also called pyridoxal-5’-phosphate-dependent reaction <ref name= "Kulik"> DOI: 10.1016/j.jmb.2005.07.014 </ref>. The catalytic cycle is reversible until the C-C bond formation <ref name= "Buller"> PMID: 27935677 </ref>. The MVC site is involved in the catalysis and regulation of substrate channeling through the hydrophobic intramolecular tunnel. For in vitro, this site is involved in equilibrium distribution of the intermediates formed during the serine reaction. Tryptophan synthase is regulated by the propagation of allosteric signals via networds of noncovalent amino acid interactions. TrpS is regulated when the indole product from the alpha reaction is transferred to the beta reaction. A substitution of a surface netowork residue in the alpha reaction enhances TrpS production by controlling the opening of the indole channel and also stimulating the beta reaction <ref name= "D'Amico"> DOI: 10.3389/fmolb.2021.679915 </ref>. These regulations are necessary for the cell to efficiently use resources since tryptophan biosynthesis is an expensive process. <br /> <br /> == Relevance ==<br /> 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>.<br /> <br /> [[Image:Tryptophan_synthasesteps.JPG]]<br /> <br /> == Structural highlights ==<br /> <br /> 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.<br /> <br /> </StructureSection><br /> == References ==<br /> Miles E. W. (2001). Tryptophan synthase: a multienzyme complex with an intramolecular tunnel. Chemical record (New York, N.Y.), 1(2), 140–151. https://doi.org/10.1002/tcr.4<br /> <br /> <references/></div>

Amer Ali https://proteopedia.org/index.php?title=User:Amer_Ali/Sandbox_2&diff=3554518 User:Amer Ali/Sandbox 2 2022-04-30T02:36:46Z

<p>Amer Ali: </p> <hr /> <div>== Tryptophan Synthase ==<br /> <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=''><br /> <br /> == Introduction ==<br /> Tryptophan synthase (TrpS) is an enzyme mainly found in bacteria, plants, and fungi <ref name= "Kulik"> DOI: 10.1016/j.jmb.2005.07.014 </ref>. TrpS must be functional for pathogenic bacteria in macrophages to survive, and it is used as a way to avoid host immune response. Tryptophan is necessary for bacteria and lower eukaryotic organisms for protein synthesis. Salmonella typhimurium and Escherichia coli serve as model organisms for the understanding of TrpS processes and structure <ref name= "Kulik"> DOI: 10.1016/j.jmb.2005.07.014 </ref>.<br /> <br /> == Structure ==<br /> 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>.<br /> <br /> <br /> == Function ==<br /> TrpS main function is to catalyze the last two steps in tryptophan biosynthesis. Reactions take place at the active sites of the alpha and beta subunit. The alpha reaction, or TrpA, catalyzes the reaction involving indole-3-glycerol phosphate (IGP) cleavage, and the products made are indole and D-glyceraldehyde 3-phosphate. The alpha reaction is done through general acid-base catalysis <ref name= "Kulik"> DOI: 10.1016/j.jmb.2005.07.014 </ref>. The TrpA active site is located at the top of the central beta-barrel with two acidic residues, Glu and Asp, involved in the acid-base catalysis <ref name= "Michalska"> PMID: 31316809 </ref>. Indole will diffuse through the hydrophobic intramolecular tunnel that leads to the active site of the beta subunit. <br /> TrpB is a type II PLP-dependent enzyme with N- and C-terminal domains, and the TrpB active site is located in a cleft between these two domains that has the PLP cofactor <ref name= "Michalska"> PMID: 31316809 </ref>.The N-terminal is the communication domain which helps coordinate the activity in TrpA and TrpB active sites. beta reaction condenses the indole with the L-serine substrate to make L-tryptophan and water. The beta reaction is also called pyridoxal-5’-phosphate-dependent reaction <ref name= "Kulik"> DOI: 10.1016/j.jmb.2005.07.014 </ref>. The catalytic cycle is reversible until the C-C bond formation <ref name= "Buller"> PMID: 27935677 </ref>. The MVC site is involved in the catalysis and regulation of substrate channeling through the hydrophobic intramolecular tunnel. For in vitro, this site is involved in equilibrium distribution of the intermediates formed during the serine reaction. Tryptophan synthase is regulated by the propagation of allosteric signals via networds of noncovalent amino acid interactions. TrpS is regulated when the indole product from the alpha reaction is transferred to the beta reaction. A substitution of a surface netowork residue in the alpha reaction enhances TrpS production by controlling the opening of the indole channel and also stimulating the beta reaction <ref name= "D'Amico"> DOI: 10.3389/fmolb.2021.679915 </ref>. These regulations are necessary for the cell to efficiently use resources since tryptophan biosynthesis is an expensive process. <br /> <br /> == Relevance ==<br /> 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>.<br /> <br /> [[Image:Tryptophan_synthasesteps.jpg]]<br /> <br /> == Structural highlights ==<br /> <br /> 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.<br /> <br /> </StructureSection><br /> == References ==<br /> Miles E. W. (2001). Tryptophan synthase: a multienzyme complex with an intramolecular tunnel. Chemical record (New York, N.Y.), 1(2), 140–151. https://doi.org/10.1002/tcr.4<br /> <br /> <references/></div>

Amer Ali https://proteopedia.org/index.php?title=User:Amer_Ali/Sandbox_2&diff=3554517 User:Amer Ali/Sandbox 2 2022-04-30T02:35:31Z

<p>Amer Ali: </p> <hr /> <div>== Tryptophan Synthase ==<br /> <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=''><br /> <br /> == Introduction ==<br /> Tryptophan synthase (TrpS) is an enzyme mainly found in bacteria, plants, and fungi <ref name= "Kulik"> DOI: 10.1016/j.jmb.2005.07.014 </ref>. TrpS must be functional for pathogenic bacteria in macrophages to survive, and it is used as a way to avoid host immune response. Tryptophan is necessary for bacteria and lower eukaryotic organisms for protein synthesis. Salmonella typhimurium and Escherichia coli serve as model organisms for the understanding of TrpS processes and structure <ref name= "Kulik"> DOI: 10.1016/j.jmb.2005.07.014 </ref>.<br /> <br /> == Structure ==<br /> 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>.<br /> <br /> <br /> == Function ==<br /> TrpS main function is to catalyze the last two steps in tryptophan biosynthesis. Reactions take place at the active sites of the alpha and beta subunit. The alpha reaction, or TrpA, catalyzes the reaction involving indole-3-glycerol phosphate (IGP) cleavage, and the products made are indole and D-glyceraldehyde 3-phosphate. The alpha reaction is done through general acid-base catalysis <ref name= "Kulik"> DOI: 10.1016/j.jmb.2005.07.014 </ref>. The TrpA active site is located at the top of the central beta-barrel with two acidic residues, Glu and Asp, involved in the acid-base catalysis <ref name= "Michalska"> PMID: 31316809 </ref>. Indole will diffuse through the hydrophobic intramolecular tunnel that leads to the active site of the beta subunit. <br /> TrpB is a type II PLP-dependent enzyme with N- and C-terminal domains, and the TrpB active site is located in a cleft between these two domains that has the PLP cofactor <ref name= "Michalska"> PMID: 31316809 </ref>.The N-terminal is the communication domain which helps coordinate the activity in TrpA and TrpB active sites. beta reaction condenses the indole with the L-serine substrate to make L-tryptophan and water. The beta reaction is also called pyridoxal-5’-phosphate-dependent reaction <ref name= "Kulik"> DOI: 10.1016/j.jmb.2005.07.014 </ref>. The catalytic cycle is reversible until the C-C bond formation <ref name= "Buller"> PMID: 27935677 </ref>. The MVC site is involved in the catalysis and regulation of substrate channeling through the hydrophobic intramolecular tunnel. For in vitro, this site is involved in equilibrium distribution of the intermediates formed during the serine reaction. Tryptophan synthase is regulated by the propagation of allosteric signals via networds of noncovalent amino acid interactions. TrpS is regulated when the indole product from the alpha reaction is transferred to the beta reaction. A substitution of a surface netowork residue in the alpha reaction enhances TrpS production by controlling the opening of the indole channel and also stimulating the beta reaction <ref name= "D'Amico"> DOI: 10.3389/fmolb.2021.679915 </ref>. These regulations are necessary for the cell to efficiently use resources since tryptophan biosynthesis is an expensive process. <br /> <br /> == Relevance ==<br /> 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>.<br /> <br /> [[Image:Tryptophan synthasesteps.jpg]]<br /> <br /> == Structural highlights ==<br /> <br /> 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.<br /> <br /> </StructureSection><br /> == References ==<br /> Miles E. W. (2001). Tryptophan synthase: a multienzyme complex with an intramolecular tunnel. Chemical record (New York, N.Y.), 1(2), 140–151. https://doi.org/10.1002/tcr.4<br /> <br /> <references/></div>

Amer Ali https://proteopedia.org/index.php?title=File:Tryptophan_synthasesteps.JPG&diff=3554515 File:Tryptophan synthasesteps.JPG 2022-04-30T02:33:27Z

<p>Amer Ali: {{Unicode|}}</p> <hr /> <div>== Summary ==<br /> {{Unicode|}}<br /> == Licensing ==<br /> {{cc-by-3.0}}</div>

Amer Ali https://proteopedia.org/index.php?title=User:Amer_Ali/Sandbox_2&diff=3554511 User:Amer Ali/Sandbox 2 2022-04-30T02:27:16Z

<p>Amer Ali: </p> <hr /> <div>== Tryptophan Synthase ==<br /> <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=''><br /> <br /> == Introduction ==<br /> Tryptophan synthase (TrpS) is an enzyme mainly found in bacteria, plants, and fungi <ref name= "Kulik"> DOI: 10.1016/j.jmb.2005.07.014 </ref>. TrpS must be functional for pathogenic bacteria in macrophages to survive, and it is used as a way to avoid host immune response. Tryptophan is necessary for bacteria and lower eukaryotic organisms for protein synthesis. Salmonella typhimurium and Escherichia coli serve as model organisms for the understanding of TrpS processes and structure <ref name= "Kulik"> DOI: 10.1016/j.jmb.2005.07.014 </ref>.<br /> <br /> == Structure ==<br /> 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>.<br /> <br /> <br /> == Function ==<br /> TrpS main function is to catalyze the last two steps in tryptophan biosynthesis. Reactions take place at the active sites of the alpha and beta subunit. The alpha reaction, or TrpA, catalyzes the reaction involving indole-3-glycerol phosphate (IGP) cleavage, and the products made are indole and D-glyceraldehyde 3-phosphate. The alpha reaction is done through general acid-base catalysis <ref name= "Kulik"> DOI: 10.1016/j.jmb.2005.07.014 </ref>. The TrpA active site is located at the top of the central beta-barrel with two acidic residues, Glu and Asp, involved in the acid-base catalysis <ref name= "Michalska"> PMID: 31316809 </ref>. Indole will diffuse through the hydrophobic intramolecular tunnel that leads to the active site of the beta subunit. <br /> TrpB is a type II PLP-dependent enzyme with N- and C-terminal domains, and the TrpB active site is located in a cleft between these two domains that has the PLP cofactor <ref name= "Michalska"> PMID: 31316809 </ref>.The N-terminal is the communication domain which helps coordinate the activity in TrpA and TrpB active sites. beta reaction condenses the indole with the L-serine substrate to make L-tryptophan and water. The beta reaction is also called pyridoxal-5’-phosphate-dependent reaction <ref name= "Kulik"> DOI: 10.1016/j.jmb.2005.07.014 </ref>. The catalytic cycle is reversible until the C-C bond formation <ref name= "Buller"> PMID: 27935677 </ref>. The MVC site is involved in the catalysis and regulation of substrate channeling through the hydrophobic intramolecular tunnel. For in vitro, this site is involved in equilibrium distribution of the intermediates formed during the serine reaction. Tryptophan synthase is regulated by the propagation of allosteric signals via networds of noncovalent amino acid interactions. TrpS is regulated when the indole product from the alpha reaction is transferred to the beta reaction. A substitution of a surface netowork residue in the alpha reaction enhances TrpS production by controlling the opening of the indole channel and also stimulating the beta reaction <ref name= "D'Amico"> DOI: 10.3389/fmolb.2021.679915 </ref>. These regulations are necessary for the cell to efficiently use resources since tryptophan biosynthesis is an expensive process. <br /> <br /> == Relevance ==<br /> 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>.<br /> <br /> == Structural highlights ==<br /> <br /> 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.<br /> <br /> </StructureSection><br /> == References ==<br /> Miles E. W. (2001). Tryptophan synthase: a multienzyme complex with an intramolecular tunnel. Chemical record (New York, N.Y.), 1(2), 140–151. https://doi.org/10.1002/tcr.4<br /> <br /> <references/></div>

Amer Ali https://proteopedia.org/index.php?title=User:Amer_Ali/Sandbox_2&diff=3554509 User:Amer Ali/Sandbox 2 2022-04-30T02:25:59Z

<p>Amer Ali: New page: == Tryptophan Synthase == <StructureSection load='1wbj' size='340' side='right' caption='Tryptophan synthase structure with alpha subunit (outer turqoise and light blue) and beta subunit (...</p> <hr /> <div>== Tryptophan Synthase ==<br /> <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) ' scene=''><br /> <br /> == Introduction ==<br /> Tryptophan synthase (TrpS) is an enzyme mainly found in bacteria, plants, and fungi <ref name= "Kulik"> DOI: 10.1016/j.jmb.2005.07.014 </ref>. TrpS must be functional for pathogenic bacteria in macrophages to survive, and it is used as a way to avoid host immune response. Tryptophan is necessary for bacteria and lower eukaryotic organisms for protein synthesis. Salmonella typhimurium and Escherichia coli serve as model organisms for the understanding of TrpS processes and structure <ref name= "Kulik"> DOI: 10.1016/j.jmb.2005.07.014 </ref>.<br /> <br /> == Structure ==<br /> 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>.<br /> <br /> <br /> == Function ==<br /> TrpS main function is to catalyze the last two steps in tryptophan biosynthesis. Reactions take place at the active sites of the alpha and beta subunit. The alpha reaction, or TrpA, catalyzes the reaction involving indole-3-glycerol phosphate (IGP) cleavage, and the products made are indole and D-glyceraldehyde 3-phosphate. The alpha reaction is done through general acid-base catalysis <ref name= "Kulik"> DOI: 10.1016/j.jmb.2005.07.014 </ref>. The TrpA active site is located at the top of the central beta-barrel with two acidic residues, Glu and Asp, involved in the acid-base catalysis <ref name= "Michalska"> PMID: 31316809 </ref>. Indole will diffuse through the hydrophobic intramolecular tunnel that leads to the active site of the beta subunit. <br /> TrpB is a type II PLP-dependent enzyme with N- and C-terminal domains, and the TrpB active site is located in a cleft between these two domains that has the PLP cofactor <ref name= "Michalska"> PMID: 31316809 </ref>.The N-terminal is the communication domain which helps coordinate the activity in TrpA and TrpB active sites. beta reaction condenses the indole with the L-serine substrate to make L-tryptophan and water. The beta reaction is also called pyridoxal-5’-phosphate-dependent reaction <ref name= "Kulik"> DOI: 10.1016/j.jmb.2005.07.014 </ref>. The catalytic cycle is reversible until the C-C bond formation <ref name= "Buller"> PMID: 27935677 </ref>. The MVC site is involved in the catalysis and regulation of substrate channeling through the hydrophobic intramolecular tunnel. For in vitro, this site is involved in equilibrium distribution of the intermediates formed during the serine reaction. Tryptophan synthase is regulated by the propagation of allosteric signals via networds of noncovalent amino acid interactions. TrpS is regulated when the indole product from the alpha reaction is transferred to the beta reaction. A substitution of a surface netowork residue in the alpha reaction enhances TrpS production by controlling the opening of the indole channel and also stimulating the beta reaction <ref name= "D'Amico"> DOI: 10.3389/fmolb.2021.679915 </ref>. These regulations are necessary for the cell to efficiently use resources since tryptophan biosynthesis is an expensive process. <br /> <br /> == Relevance ==<br /> 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>.<br /> <br /> == Structural highlights ==<br /> <br /> 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.<br /> <br /> </StructureSection><br /> == References ==<br /> Miles E. W. (2001). Tryptophan synthase: a multienzyme complex with an intramolecular tunnel. Chemical record (New York, N.Y.), 1(2), 140–151. https://doi.org/10.1002/tcr.4<br /> <br /> <references/></div>

Amer Ali https://proteopedia.org/index.php?title=User:Amer_Ali&diff=3554508 User:Amer Ali 2022-04-30T02:12:50Z

<p>Amer Ali: </p> <hr /> <div>* Full Real Name: Amer Ali<br /> <br /> * Position: Student<br /> <br /> * Institution (NO ABBREVIATIONS): Maryville University<br /> <br /> * City, State/Province, Country: St. Louis, Missouri<br /> <br /> * Field of Expertise or Study: Student<br /> <br /> <br /> [[User:Amer Ali/Sandbox 1]]<br /> <br /> [[User:Amer Ali/Sandbox 2]]</div>

Amer Ali https://proteopedia.org/index.php?title=User:Amer_Ali/Sandbox_1&diff=3554507 User:Amer Ali/Sandbox 1 2022-04-30T02:05:57Z

<p>Amer Ali: </p> <hr /> <div>== Tryptophan Synthase ==<br /> <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) ' scene=''><br /> <br /> == Introduction ==<br /> Tryptophan synthase (TrpS) is an enzyme mainly found in bacteria, plants, and fungi <ref name= "Kulik"> DOI: 10.1016/j.jmb.2005.07.014 </ref>. TrpS must be functional for pathogenic bacteria in macrophages to survive, and it is used as a way to avoid host immune response. Tryptophan is necessary for bacteria and lower eukaryotic organisms for protein synthesis. Salmonella typhimurium and Escherichia coli serve as model organisms for the understanding of TrpS processes and structure <ref name= "Kulik"> DOI: 10.1016/j.jmb.2005.07.014 </ref>.<br /> <br /> == Function ==<br /> 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 <ref name= "Miles"> DOI: 10.1002/tcr.4</ref>. 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>.<br /> <br /> <br /> == Disease ==<br /> <br /> == Relevance ==<br /> <br /> == Structural highlights ==<br /> <br /> 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.<br /> <br /> </StructureSection><br /> == References ==<br /> <references/></div>

Amer Ali https://proteopedia.org/index.php?title=User:Amer_Ali/Sandbox_1&diff=3554506 User:Amer Ali/Sandbox 1 2022-04-30T02:01:08Z

<p>Amer Ali: </p> <hr /> <div>== Tryptophan Synthase ==<br /> <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) ' scene=''><br /> <br /> == Introduction ==<br /> Tryptophan synthase (TrpS) is an enzyme mainly found in bacteria, plants, and fungi <ref name= "Kulik"> DOI: 10.1016/j.jmb.2005.07.014 </ref>. TrpS must be functional for pathogenic bacteria in macrophages to survive, and it is used as a way to avoid host immune response. Tryptophan is necessary for bacteria and lower eukaryotic organisms for protein synthesis. Salmonella typhimurium and Escherichia coli serve as model organisms for the understanding of TrpS processes and structure <ref name= "Kulik"> DOI: 10.1016/j.jmb.2005.07.014 </ref>.<br /> <br /> == Function ==<br /> 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> <ref name= "Dunn"> DOI: 10.1007/978-1-4614-1533-6244 </ref> (Dunn, 2013). For regulation, TrpA and TrpB cycle between low-activity open conformation and a high-activity closed state. This is done by the bining 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>.<br /> <br /> <br /> == Disease ==<br /> <br /> == Relevance ==<br /> <br /> == Structural highlights ==<br /> <br /> 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.<br /> <br /> </StructureSection><br /> == References ==<br /> <references/></div>

Amer Ali https://proteopedia.org/index.php?title=User:Amer_Ali/Sandbox_1&diff=3554505 User:Amer Ali/Sandbox 1 2022-04-30T01:40:48Z

<p>Amer Ali: New page: ==Your Heading Here (maybe something like 'Structure')== <StructureSection load='1stp' size='340' side='right' caption='Caption for this structure' scene=''> This is a default text for you...</p> <hr /> <div>==Your Heading Here (maybe something like 'Structure')==<br /> <StructureSection load='1stp' size='340' side='right' caption='Caption for this structure' scene=''><br /> This is a default text for your page '''Amer Ali/Sandbox 1'''. Click above on '''edit this page''' to modify. Be careful with the &lt; and &gt; signs.<br /> You may include any references to papers as in: the use of JSmol in Proteopedia <ref>DOI 10.1002/ijch.201300024</ref> or to the article describing Jmol <ref>PMID:21638687</ref> to the rescue.<br /> <br /> == Function ==<br /> <br /> == Disease ==<br /> <br /> == Relevance ==<br /> <br /> == Structural highlights ==<br /> <br /> 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.<br /> <br /> </StructureSection><br /> == References ==<br /> <references/></div>

Amer Ali https://proteopedia.org/index.php?title=User:Amer_Ali&diff=3554504 User:Amer Ali 2022-04-30T01:40:10Z

<p>Amer Ali: </p> <hr /> <div>* Full Real Name: Amer Ali<br /> <br /> * Position: Student<br /> <br /> * Institution (NO ABBREVIATIONS): Maryville University<br /> <br /> * City, State/Province, Country: St. Louis, Missouri<br /> <br /> * Field of Expertise or Study: Student<br /> <br /> <br /> [[User:Amer Ali/Sandbox 1]]</div>

Amer Ali https://proteopedia.org/index.php?title=Tryptophan_synthase&diff=3554503 Tryptophan synthase 2022-04-30T00:33:20Z

<p>Amer Ali: </p> <hr /> <div><StructureSection load='' size='350' side='right' caption='Tryptophan synthase α subunit (yellow, salmon) and β subunit (cyan, green) of the α2β2 tetramer complex with pyridoxal-phosphate, glycerol-3-phosphate and Na+ ion (purple) [[1wbj]]' scene='52/525189/Cv/5'><br /> <br /> == Function ==<br /> '''Tryptophan synthase''' (TrpS) is an α2β2 tetramer participating in the biosynthesis of tryptophan<ref>PMID:11893063</ref>. TrpS '''α subunit''' catalyzes the formation of indole and glyceraldehyde-3-phosphate (G3P) from indole-3-glycerol phosphate (IGP). The '''β subunit''' catalyzes in a pyridoxal-phosphate (PLP) dependent reaction the formation of tryptophan (Trp) from indole and serine. The diffusion of indole from the α to the β subunit is facilitated via a hydrophobic channel connecting the subunits. <br /> <br /> == Relevance ==<br /> TrpS is not found in animals hence it is tested as a possible drug target for tuberculosis, ocular and genital infections, cryptosporidiosis and as herbicide<ref>PMID:19430702</ref>.<br /> <br /> == Structural highlights ==<br /> The <scene name='52/525189/Cv/6'>active site</scene> of TrpS subunit α contains the catalytic residues Glu and Asp<ref>PMID:16120446</ref>. Water molecules are shown as red spheres.<br /> ==3D structures of tryptophan synthase==<br /> [[Tryptophan synthase 3D structures]]<br /> <br /> </StructureSection><br /> <br /> == References ==<br /> <references/><br /> [[Category:Topic Page]]</div>

Amer Ali https://proteopedia.org/index.php?title=Tryptophan_synthase&diff=3554502 Tryptophan synthase 2022-04-30T00:31:35Z

<p>Amer Ali: </p> <hr /> <div><StructureSection load='' size='350' side='right' caption='Tryptophan synthase α subunit (yellow, salmon) and β subunit (cyan, green) of the α2β2 tetramer complex with pyridoxal-phosphate, glycerol-3-phosphate and Na+ ion (purple) [[1wbj]]' scene='52/525189/Cv/5'><br /> <br /> == Introduction ==<br /> <br /> <br /> == Function ==<br /> '''Tryptophan synthase''' (TrpS) is an α2β2 tetramer participating in the biosynthesis of tryptophan<ref>PMID:11893063</ref>. TrpS '''α subunit''' catalyzes the formation of indole and glyceraldehyde-3-phosphate (G3P) from indole-3-glycerol phosphate (IGP). The '''β subunit''' catalyzes in a pyridoxal-phosphate (PLP) dependent reaction the formation of tryptophan (Trp) from indole and serine. The diffusion of indole from the α to the β subunit is facilitated via a hydrophobic channel connecting the subunits. <br /> <br /> == Relevance ==<br /> TrpS is not found in animals hence it is tested as a possible drug target for tuberculosis, ocular and genital infections, cryptosporidiosis and as herbicide<ref>PMID:19430702</ref>.<br /> <br /> == Structural highlights ==<br /> The <scene name='52/525189/Cv/6'>active site</scene> of TrpS subunit α contains the catalytic residues Glu and Asp<ref>PMID:16120446</ref>. Water molecules are shown as red spheres.<br /> ==3D structures of tryptophan synthase==<br /> [[Tryptophan synthase 3D structures]]<br /> <br /> </StructureSection><br /> <br /> == References ==<br /> ↑Abrahams, K. A., Cox, J., Fütterer, K., Rullas, J., Ortega-Muro, F., Loman, N. J., Moynihan, P. J., Pérez-Herrán, E., Jiménez, E., Esquivias, J., Barros, D., Ballell, L., Alemparte, C., & Besra, G. S. (2017). Inhibiting mycobacterial tryptophan synthase by targeting the inter-subunit interface. Scientific reports, 7(1), 9430. <br /> <br /> <references/><br /> [[Category:Topic Page]]</div>

Amer Ali https://proteopedia.org/index.php?title=Tryptophan_synthase&diff=3554501 Tryptophan synthase 2022-04-30T00:30:10Z

<p>Amer Ali: </p> <hr /> <div><StructureSection load='' size='350' side='right' caption='Tryptophan synthase α subunit (yellow, salmon) and β subunit (cyan, green) of the α2β2 tetramer complex with pyridoxal-phosphate, glycerol-3-phosphate and Na+ ion (purple) [[1wbj]]' scene='52/525189/Cv/5'><br /> <br /> == Introduction ==<br /> <br /> <br /> == Function ==<br /> '''Tryptophan synthase''' (TrpS) is an α2β2 tetramer participating in the biosynthesis of tryptophan<ref>PMID:11893063</ref>. TrpS '''α subunit''' catalyzes the formation of indole and glyceraldehyde-3-phosphate (G3P) from indole-3-glycerol phosphate (IGP). The '''β subunit''' catalyzes in a pyridoxal-phosphate (PLP) dependent reaction the formation of tryptophan (Trp) from indole and serine. The diffusion of indole from the α to the β subunit is facilitated via a hydrophobic channel connecting the subunits. <br /> <br /> == Relevance ==<br /> TrpS is not found in animals hence it is tested as a possible drug target for tuberculosis, ocular and genital infections, cryptosporidiosis and as herbicide<ref>PMID:19430702</ref>.<br /> <br /> == Structural highlights ==<br /> The <scene name='52/525189/Cv/6'>active site</scene> of TrpS subunit α contains the catalytic residues Glu and Asp<ref>PMID:16120446</ref>. Water molecules are shown as red spheres.<br /> ==3D structures of tryptophan synthase==<br /> [[Tryptophan synthase 3D structures]]<br /> <br /> </StructureSection><br /> <br /> == References ==<br /> Abrahams, K. A., Cox, J., Fütterer, K., Rullas, J., Ortega-Muro, F., Loman, N. J., Moynihan, P. J., Pérez-Herrán, E., Jiménez, E., Esquivias, J., Barros, D., Ballell, L., Alemparte, C., & Besra, G. S. (2017). Inhibiting mycobacterial tryptophan synthase by targeting the inter-subunit interface. Scientific reports, 7(1), 9430. <br /> <br /> <references/><br /> [[Category:Topic Page]]</div>

Amer Ali https://proteopedia.org/index.php?title=Tryptophan_synthase&diff=3554500 Tryptophan synthase 2022-04-30T00:19:14Z

<p>Amer Ali: </p> <hr /> <div><StructureSection load='' size='350' side='right' caption='Tryptophan synthase α subunit (yellow, salmon) and β subunit (cyan, green) of the α2β2 tetramer complex with pyridoxal-phosphate, glycerol-3-phosphate and Na+ ion (purple) [[1wbj]]' scene='52/525189/Cv/5'><br /> <br /> == Introduction ==<br /> <br /> <br /> == Function ==<br /> '''Tryptophan synthase''' (TrpS) is an α2β2 tetramer participating in the biosynthesis of tryptophan<ref>PMID:11893063</ref>. TrpS '''α subunit''' catalyzes the formation of indole and glyceraldehyde-3-phosphate (G3P) from indole-3-glycerol phosphate (IGP). The '''β subunit''' catalyzes in a pyridoxal-phosphate (PLP) dependent reaction the formation of tryptophan (Trp) from indole and serine. The diffusion of indole from the α to the β subunit is facilitated via a hydrophobic channel connecting the subunits. <br /> <br /> == Relevance ==<br /> TrpS is not found in animals hence it is tested as a possible drug target for tuberculosis, ocular and genital infections, cryptosporidiosis and as herbicide<ref>PMID:19430702</ref>.<br /> <br /> == Structural highlights ==<br /> The <scene name='52/525189/Cv/6'>active site</scene> of TrpS subunit α contains the catalytic residues Glu and Asp<ref>PMID:16120446</ref>. Water molecules are shown as red spheres.<br /> ==3D structures of tryptophan synthase==<br /> [[Tryptophan synthase 3D structures]]<br /> <br /> </StructureSection><br /> <br /> == References ==<br /> <references/><br /> [[Category:Topic Page]]</div>

Amer Ali