5YPV

Crystal structure of FabD from Acinetobacter baumannii

5YPV の概要

• エントリーDOI: 10.2210/pdb5ypv/pdb
• 分子名称: Malonyl CoA-acyl carrier protein transacylase (2 entities in total)
• 機能のキーワード: transacylase, transferase
• 由来する生物種: Acinetobacter baumannii
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 32843.36

構造登録者

Lee, W.C.,Kim, Y. (登録日: 2017-11-03, 公開日: 2018-11-07, 最終更新日: 2024-03-27)

主引用文献

Lee, W.C.,Park, J.,Balasubramanian, P.K.,Kim, Y.
Elucidation of the crystal structure of FabD from the multidrug-resistant bacterium Acinetobacter baumannii.
Biochem.Biophys.Res.Commun., 505:208-214, 2018

PubMed Abstract: Bacterial fatty acid synthesis (FAS) has been extensively studied as a potential target of antimicrobials. In FAS, FabD mediates transacylation of the malonyl group from malonyl-CoA to acyl-carrier protein (ACP). The mounting threat of nosocomial infection by multidrug-resistant Acinetobacter baumannii warrants a deeper understanding of its essential cellular mechanisms, which could lead to effective control of this highly competent pathogen. The molecular mechanisms involved in A. baumannii FAS are poorly understood, and recent research has suggested that Pseudomonas aeruginosa, a closely related nosocomial pathogen of A. baumannii, utilizes FAS to produce virulence factors. In this study, we solved the crystal structure of A. baumannii FabD (AbFabD) to provide a platform for the development of new antibacterial agents. Analysis of the structure of AbFabD confirmed the presence of highly conserved active site residues among bacterial homologs. Binding constants between AbFabD variants and A. baumannii ACP (AbACP) revealed critical conserved residues Lys195 and Lys200 involved in AbACP binding. Computational docking of a potential inhibitor, trifluoperazine, revealed a unique inhibitor-binding pocket near the substrate-binding site. The structural study presented herein will be useful for the structure-based design of potent AbFabD inhibitors.

PubMed: 30243724
DOI: 10.1016/j.bbrc.2018.09.079

実験手法

X-RAY DIFFRACTION (1.67 Å)