4WNB

Crystal structure of the ChsH1-ChsH2 complex from Mycobacterium tuberculosis bound to 3-OPC-CoA

「4W7B」から置き換えられました

4WNB の概要

• エントリーDOI: 10.2210/pdb4wnb/pdb
• 分子名称: Hydratase ChsH2, Hydratase ChsH1, CADMIUM ION, ... (6 entities in total)
• 機能のキーワード: lyase
• 由来する生物種: Mycobacterium tuberculosis KZN 4207; 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 35538.68

構造登録者

Guja, K.E.,Yang, M.,Sampson, N.,Garcia-Diaz, M. (登録日: 2014-10-11, 公開日: 2014-10-29, 最終更新日: 2023-12-27)

主引用文献

Yang, M.,Guja, K.E.,Thomas, S.T.,Garcia-Diaz, M.,Sampson, N.S.
A Distinct MaoC-like Enoyl-CoA Hydratase Architecture Mediates Cholesterol Catabolism in Mycobacterium tuberculosis.
Acs Chem.Biol., 9:2632-2645, 2014

PubMed Abstract: The Mycobacterium tuberculosis (Mtb) igr operon plays an essential role in Mtb cholesterol metabolism, which is critical for pathogenesis during the latent stage of Mtb infection. Here we report the first structure of a heterotetrameric MaoC-like enoyl-CoA hydratase, ChsH1-ChsH2, which is encoded by two adjacent genes from the igr operon. We demonstrate that ChsH1-ChsH2 catalyzes the hydration of a steroid enoyl-CoA, 3-oxo-4,17-pregnadiene-20-carboxyl-CoA, in the modified β-oxidation pathway for cholesterol side chain degradation. The ligand-bound and apoenzyme structures of ChsH1-ChsH2(N) reveal an unusual, modified hot-dog fold with a severely truncated central α-helix that creates an expanded binding site to accommodate the bulkier steroid ring system. The structures show quaternary structure shifts that accommodate the four rings of the steroid substrate and offer an explanation for why the unusual heterotetrameric assembly is utilized for hydration of this steroid. The unique αβ heterodimer architecture utilized by ChsH1-ChsH2 to bind its distinctive substrate highlights an opportunity for the development of new antimycobacterial drugs that target a pathway specific to Mtb.

PubMed: 25203216
DOI: 10.1021/cb500232h

実験手法

X-RAY DIFFRACTION (1.76 Å)