PDBsum entry 4b6c

Isomerase

PDB id: 4b6c

Contents

Protein chains

161 a.a.

Ligands

B5U ×2

Metals

_NA ×2

Waters ×112

References listed in PDB file

Key reference

• Title: Aminopyrazinamides: novel and specific gyrb inhibitors that kill replicating and nonreplicating mycobacterium tuberculosis.
• Authors: P.S.Shirude, P.Madhavapeddi, J.A.Tucker, K.Murugan, V.Patil, H.Basavarajappa, A.V.Raichurkar, V.Humnabadkar, S.Hussein, S.Sharma, V.K.Ramya, C.B.Narayan, T.S.Balganesh, V.K.Sambandamurthy.
• Ref.: Acs Chem Biol, 2013, 8, 519-523. [DOI no: 10.1021/cb300510w]
• PubMed id: 23268609

Abstract

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.