Sun, QG; Li, XJ; Perez, LM; Shi, WL; Zhang, Y; Sacchettini, JC in [Sun, Qingan; Li, Xiaojun; Sacchettini, James C.] Texas A&M Univ, Dept Biochem & Biophys, College Stn, TX 77843 USA; [Perez, Lisa M.] Texas A&M Univ, Lab Mol Simulat, College Stn, TX USA; [Shi, Wanliang; Zhang, Ying] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Mol Microbiol & Immunol, Baltimore, MD 21205 USA published The molecular basis of pyrazinamide activity on Mycobacterium tuberculosis PanD in 2020, Cited 30. COA of Formula: C5H4N2O2. The Name is Pyrazine-2-carboxylic acid. Through research, I have a further understanding and discovery of 98-97-5.
Pyrazinamide has been a mainstay in the multidrug regimens used to treat tuberculosis. It is active against the persistent, non-replicating mycobacteria responsible for the protracted therapy required to cure tuberculosis. Pyrazinamide is a pro-drug that is converted into pyrazinoic acid (POA) by pyrazinamidase, however, the exact target of the drug has been difficult to determine. Here we show the enzyme PanD binds POA in its active site in a manner consistent with competitive inhibition. The active site is not directly accessible to the inhibitor, suggesting the protein must undergo a conformational change to bind the inhibitor. This is consistent with the slow binding kinetics we determined for POA. Drug-resistant mutations cluster near loops that lay on top of the active site. These resistant mutants show reduced affinity and residence time of POA consistent with a model where resistance occurs by destabilizing the closed conformation of the active site. The important tuberculosis drug pyrazinamide (PZA) is converted to its active form pyrazinoic acid (POA) in Mycobacterium tuberculosis (Mtb). Here the authors identify the pantothenate biosynthesis pathway enzyme aspartate decarboxylase (PanD) as the target of PZA and determine the POA bound Mtb PanD crystal structure.
COA of Formula: C5H4N2O2. Bye, fridends, I hope you can learn more about C5H4N2O2, If you have any questions, you can browse other blog as well. See you lster.
Reference:
Patent; Chevron Research Company; US4732894; (1988); A;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem