Structural highlights
Function
[GYRB_MYCSM] DNA gyrase negatively supercoils closed circular double-stranded DNA in an ATP-dependent manner and also catalyzes the interconversion of other topological isomers of double-stranded DNA rings, including catenanes and knotted rings.
Publication Abstract from PubMed
Aminopyrazinamides originated from a high throughput screen targeting the Mycobacterium smegmatis (Msm) GyrB ATPase. This series displays chemical tractability, robust structure-activity relationship, and potent antitubercular activity. The crystal structure of Msm GyrB in complex with one of the aminopyrazinamides revealed promising attributes of specificity against other broad spectrum pathogens and selectivity against eukaryotic kinases due to novel interactions at hydrophobic pocket, unlike other known GyrB inhibitors. The aminopyrazinamides display excellent mycobacterial kill under in vitro, intracellular, and hypoxic conditions.
Aminopyrazinamides: Novel and Specific GyrB Inhibitors that Kill Replicating and Nonreplicating Mycobacterium tuberculosis.,Shirude PS, Madhavapeddi P, Tucker JA, Murugan K, Patil V, Basavarajappa H, Raichurkar AV, Humnabadkar V, Hussein S, Sharma S, Ramya VK, Narayan CB, Balganesh TS, Sambandamurthy VK ACS Chem Biol. 2012 Dec 31. PMID:23268609[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Shirude PS, Madhavapeddi P, Tucker JA, Murugan K, Patil V, Basavarajappa H, Raichurkar AV, Humnabadkar V, Hussein S, Sharma S, Ramya VK, Narayan CB, Balganesh TS, Sambandamurthy VK. Aminopyrazinamides: Novel and Specific GyrB Inhibitors that Kill Replicating and Nonreplicating Mycobacterium tuberculosis. ACS Chem Biol. 2012 Dec 31. PMID:23268609 doi:http://dx.doi.org/10.1021/cb300510w
