5SYI

Structure of D141A variant of B. pseudomallei KatG complexed with INH

「4KA6」から置き換えられました

5SYI の概要

• エントリーDOI: 10.2210/pdb5syi/pdb
• 関連するPDBエントリー: 5L02 5L05 5SW4 5SW5 5SW6 5SX0 5SX1 5SX2 5SX3 5SX6 5SX7 5SXQ 5SXR 5SXS 5SXT 5SXX 5SYH 5SYJ 5SYK 5SYL 5SYU 5SYV 5SYW 5SYX 5SYY
• 分子名称: Catalase-peroxidase, PROTOPORPHYRIN IX CONTAINING FE, SODIUM ION, ... (9 entities in total)
• 機能のキーワード: catalase-peroxidase, katg, isoniazid, d141a variant, oxidoreductase
• 由来する生物種: Burkholderia pseudomallei (strain 1710b)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 161473.87

構造登録者

Loewen, P.C. (登録日: 2016-08-11, 公開日: 2016-09-07, 最終更新日: 2024-10-23)

主引用文献

Vidossich, P.,Loewen, P.C.,Carpena, X.,Fiorin, G.,Fita, I.,Rovira, C.
Binding of the antitubercular pro-drug isoniazid in the heme access channel of catalase-peroxidase (KatG). A combined structural and metadynamics investigation.
J Phys Chem B, 118:2924-2931, 2014

PubMed Abstract: Isonicotinic acid hydrazide (isoniazid or INH) is a front line antitubercular pro-drug that is converted to its active form, isonicotinyl-NAD, by the bacterial catalase-peroxidase KatG. Understanding the role of KatG in the INH activation process has been hampered by a lack of knowledge of the actual drug binding site. In this work, we have investigated the binding of INH in the main access channel of KatG with a combination of molecular dynamics, using an enhanced-sampling technique (metadynamics), X-ray crystallography, and site-directed mutagenesis. The metadynamics simulations show that there are several weak drug binding sites along the access channel. Moreover, the simulations evidence that complete entrance to the heme active site is impeded by an aspartate residue (D141) located above the heme. This has been confirmed by structural and functional analysis of the D141A mutant, leading to the first X-ray crystallography evidence of INH at the heme access channel.

PubMed: 24568093
DOI: 10.1021/jp4123425

実験手法

X-RAY DIFFRACTION (1.7 Å)