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