Staphylococcus aureus FabI: inhibition, substrate recognition, and potential implications for in vivo essentiality.

ABSTRACT: Methicillin-resistant Staphylococcus aureus (MRSA) infections constitute a serious health threat worldwide, and novel antibiotics are therefore urgently needed. The enoyl-ACP reductase (saFabI) is essential for the S. aureus fatty acid biosynthesis and, hence, serves as an attractive drug target. We have obtained a series of snapshots of this enzyme that provide a mechanistic picture of ligand and inhibitor binding, including a dimer-tetramer transition combined with extensive conformational changes. Significantly, our results reveal key differences in ligand binding and recognition compared to orthologous proteins. The remarkable observed protein flexibility rationalizes our finding that saFabI is capable of efficiently reducing branched-chain fatty acid precursors. Importantly, branched-

SUBMITTER: Schiebel J 

PROVIDER: S-EPMC3376755 | biostudies-literature | 2012 May

REPOSITORIES: biostudies-literature