2QNX

Crystal structure of the complex between the mycobacterium beta-ketoacyl-acyl carrier protein synthase III (FABH) and 11-[(decyloxycarbonyl)dithio]-undecanoic acid

2QNX の概要

• エントリーDOI: 10.2210/pdb2qnx/pdb
• 関連するPDBエントリー: 1HNJ 1HNK 1HZP 1U6E 1U6S 2QNY 2QNZ 2QO0 2QO1
• 分子名称: 3-oxoacyl-[acyl-carrier-protein] synthase 3, O-DECYL HYDROGEN THIOCARBONATE, 11-MERCAPTOUNDECANOIC ACID, ... (4 entities in total)
• 機能のキーワード: fatty acid biosynthesis, myobacterium tuberculosis, structural basis for substrate specificity, enzyme inhibitor complex, mechanism based inhibitor, acyltransferase, lipid synthesis, multifunctional enzyme, transferase
• 由来する生物種: Mycobacterium tuberculosis
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 70680.21

構造登録者

Sachdeva, S.,Musayev, F.,Alhamadsheh, M.,Scarsdale, J.N.,Wright, H.T.,Reynolds, K.A. (登録日: 2007-07-19, 公開日: 2008-05-06, 最終更新日: 2024-10-16)

主引用文献

Sachdeva, S.,Musayev, F.N.,Alhamadsheh, M.M.,Scarsdale, J.N.,Wright, H.T.,Reynolds, K.A.
Separate Entrance and Exit Portals for Ligand Traffic in Mycobacterium tuberculosis FabH
Chem.Biol., 15:402-412, 2008

PubMed Abstract: Mycobacterium tuberculosis FabH initiates type II fatty acid synthase-catalyzed formation of the long chain (C(16)-C(22)) acyl-coenzyme A (CoA) precursors of mycolic acids, which are major constituents of the bacterial cell envelope. Crystal structures of M. tuberculosis FabH (mtFabH) show the substrate binding site to be a buried, extended L-shaped channel with only a single solvent access portal. Entrance of an acyl-CoA substrate through the solvent portal would require energetically unfavorable reptational threading of the substrate to its reactive position. Using a class of FabH inhibitors, we have tested an alternative hypothesis that FabH exists in an "open" form during substrate binding and product release, and a "closed" form in which catalysis and intermediate steps occur. This hypothesis is supported by mass spectrometric analysis of the product profile and crystal structures of complexes of mtFabH with these inhibitors.

PubMed: 18420147
DOI: 10.1016/j.chembiol.2008.03.007

実験手法

X-RAY DIFFRACTION (2.7 Å)