Structure of the Essential Mtb FadD32 Enzyme: A Promising Drug Target for Treating Tuberculosis.

ABSTRACT: Mycolic acids are indispensible lipids of Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis (TB), and contribute to the distinctive architecture and impermeability of the mycobacterial cell envelope. FadD32 plays a pivotal role in mycolic acid biosynthesis by functionally linking fatty acid synthase (FAS) and polyketide synthase (PKS) biosynthetic pathways. FadD32, a fatty acyl-AMP ligase (FAAL), represents one of the best genetically and chemically validated new TB drug targets. We have determined the three-dimensional crystal structure of Mtb FadD32 in complex with a ligand specifically designed to stabilize the catalytically active adenylate-conformation, which provides a foundation for structure-based drug design efforts against this essential p

SUBMITTER: Kuhn ML 

PROVIDER: S-EPMC4989915 | biostudies-literature | 2016 Aug

REPOSITORIES: biostudies-literature