4ALI: Crystal Structure of S. Aureus Fabi in Complex With Nadp and Triclosan (P1)

Citation:
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-chain fatty acids represent a major fraction of the S. aureus cell membrane and are crucial for its in vivo fitness. Our discovery thus addresses a long-standing controversy regarding the essentiality of the fatty acid biosynthesis pathway in S. aureus rationalizing saFabI as a drug target.
PDB ID: 4ALIDownload
MMDB ID: 99398
PDB Deposition Date: 2012/3/4
Updated in MMDB: 2012/05 
Experimental Method:
x-ray diffraction
Resolution: 2.1  Å
Source Organism:
Similar Structures:
Biological Unit for 4ALI: tetrameric; determined by author and by software (PISA)
Molecular Components in 4ALI
Label Count Molecule
Proteins (4 molecules)
4
Enoyl-[acyl-carrier-protein] Reductase [nadph]
Molecule annotation
Chemicals (13 molecules)
1
5
2
4
3
4
* Click molecule labels to explore molecular sequence information.

Citing MMDB
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