4JB6

Structure of Pseudomonas aeruginosa FabF mutant C164Q

4JB6 の概要

• エントリーDOI: 10.2210/pdb4jb6/pdb
• 関連するPDBエントリー: 4b7v
• 分子名称: 3-oxoacyl-[acyl-carrier-protein] synthase 2, POTASSIUM ION (3 entities in total)
• 機能のキーワード: fatty acid biosynthesis, transferase
• 由来する生物種: Pseudomonas aeruginosa
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 87216.20

構造登録者

Baum, B.,Lecker, L. (登録日: 2013-02-19, 公開日: 2014-03-05, 最終更新日: 2023-09-20)

主引用文献

Baum, B.,Lecker, L.S.,Zoltner, M.,Jaenicke, E.,Schnell, R.,Hunter, W.N.,Brenk, R.
Structures of Pseudomonas aeruginosa beta-ketoacyl-(acyl-carrier-protein) synthase II (FabF) and a C164Q mutant provide templates for antibacterial drug discovery and identify a buried potassium ion and a ligand-binding site that is an artefact of the crystal form.
Acta Crystallogr F Struct Biol Commun, 71:1020-1026, 2015

PubMed Abstract: Bacterial infections remain a serious health concern, in particular causing life-threatening infections of hospitalized and immunocompromised patients. The situation is exacerbated by the rise in antibacterial drug resistance, and new treatments are urgently sought. In this endeavour, accurate structures of molecular targets can support early-stage drug discovery. Here, crystal structures, in three distinct forms, of recombinant Pseudomonas aeruginosa β-ketoacyl-(acyl-carrier-protein) synthase II (FabF) are presented. This enzyme, which is involved in fatty-acid biosynthesis, has been validated by genetic and chemical means as an antibiotic target in Gram-positive bacteria and represents a potential target in Gram-negative bacteria. The structures of apo FabF, of a C164Q mutant in which the binding site is altered to resemble the substrate-bound state and of a complex with 3-(benzoylamino)-2-hydroxybenzoic acid are reported. This compound mimics aspects of a known natural product inhibitor, platensimycin, and surprisingly was observed binding outside the active site, interacting with a symmetry-related molecule. An unusual feature is a completely buried potassium-binding site that was identified in all three structures. Comparisons suggest that this may represent a conserved structural feature of FabF relevant to fold stability. The new structures provide templates for structure-based ligand design and, together with the protocols and reagents, may underpin a target-based drug-discovery project for urgently needed antibacterials.

PubMed: 26249693
DOI: 10.1107/S2053230X15010614

実験手法

X-RAY DIFFRACTION (2.4 Å)