4ALN

Crystal structure of S. aureus FabI (P32)

4ALN の概要

• エントリーDOI: 10.2210/pdb4aln/pdb
• 関連するPDBエントリー: 4ALI 4ALJ 4ALK 4ALL 4ALM
• 分子名称: ENOYL-[ACYL-CARRIER-PROTEIN] REDUCTASE [NADPH] (2 entities in total)
• 機能のキーワード: oxidoreductase, short-chain dehydrogenase/reductase superfamily, fatty acid biosynthesis, lipid synthesis
• 由来する生物種: STAPHYLOCOCCUS AUREUS
• タンパク質・核酸の鎖数: 12
• 化学式量合計: 373730.88

構造登録者

Schiebel, J.,Kisker, C. (登録日: 2012-03-04, 公開日: 2012-05-09, 最終更新日: 2023-12-20)

主引用文献

Schiebel, J.,Chang, A.,Lu, H.,Baxter, M.V.,Tonge, P.J.,Kisker, C.
Staphylococcus Aureus Fabi: Inhibition, Substrate Recognition and Potential Implications for in Vivo Essentiality
Structure, 20:802-, 2012

PubMed 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.

PubMed: 22579249
DOI: 10.1016/J.STR.2012.03.013

実験手法

X-RAY DIFFRACTION (3.05 Å)