7A7C

Cryo-EM structure of W107R after heme uptake (1heme molecule) KatG from M. tuberculosis

7A7C の概要

• エントリーDOI: 10.2210/pdb7a7c/pdb
• EMDBエントリー: 11677
• 分子名称: Catalase-peroxidase, PROTOPORPHYRIN IX CONTAINING FE (2 entities in total)
• 機能のキーワード: heme, peroxidase-catalase, metal binding protein
• 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: 161933.67

構造登録者

Blundell, T.L.,Chaplin, A.K.,Munir, A. (登録日: 2020-08-27, 公開日: 2021-01-27, 最終更新日: 2024-07-10)

主引用文献

Munir, A.,Wilson, M.T.,Hardwick, S.W.,Chirgadze, D.Y.,Worrall, J.A.R.,Blundell, T.L.,Chaplin, A.K.
Using cryo-EM to understand antimycobacterial resistance in the catalase-peroxidase (KatG) from Mycobacterium tuberculosis.
Structure, 29:899-912.e4, 2021

PubMed Abstract: Resolution advances in cryoelectron microscopy (cryo-EM) now offer the possibility to visualize structural effects of naturally occurring resistance mutations in proteins and also of understanding the binding mechanisms of small drug molecules. In Mycobacterium tuberculosis the multifunctional heme enzyme KatG is indispensable for activation of isoniazid (INH), a first-line pro-drug for treatment of tuberculosis. We present a cryo-EM methodology for structural and functional characterization of KatG and INH resistance variants. The cryo-EM structure of the 161 kDa KatG dimer in the presence of INH is reported to 2.7 Å resolution allowing the observation of potential INH binding sites. In addition, cryo-EM structures of two INH resistance variants, identified from clinical isolates, W107R and T275P, are reported. In combination with electronic absorbance spectroscopy our cryo-EM approach reveals how these resistance variants cause disorder in the heme environment preventing heme uptake and retention, providing insight into INH resistance.

PubMed: 33444527
DOI: 10.1016/j.str.2020.12.008

実験手法

ELECTRON MICROSCOPY (3.16 Å)