- EMDB-11680: Cryo-EM structure of T275P KatG from M. tuberculosis -
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データベース: EMDB / ID: EMD-11680
タイトル
Cryo-EM structure of T275P KatG from M. tuberculosis
マップデータ
試料
細胞器官・細胞要素: T275P KatG variant from M. tuberculosis
タンパク質・ペプチド: Catalase-peroxidase
機能・相同性
機能・相同性情報
oxidoreductase activity, acting on a heme group of donors, nitrogenous group as acceptor / Tolerance of reactive oxygen produced by macrophages / catalase-peroxidase / NADH binding / catalase activity / NADPH binding / positive regulation of DNA repair / peptidoglycan-based cell wall / hydrogen peroxide catabolic process / cellular response to hydrogen peroxide ...oxidoreductase activity, acting on a heme group of donors, nitrogenous group as acceptor / Tolerance of reactive oxygen produced by macrophages / catalase-peroxidase / NADH binding / catalase activity / NADPH binding / positive regulation of DNA repair / peptidoglycan-based cell wall / hydrogen peroxide catabolic process / cellular response to hydrogen peroxide / peroxidase activity / response to oxidative stress / response to antibiotic / heme binding / extracellular region / metal ion binding / plasma membrane / cytosol 類似検索 - 分子機能
Catalase-peroxidase haem / Peroxidases heam-ligand binding site / Peroxidase, active site / Peroxidases active site signature. / Plant heme peroxidase family profile. / Haem peroxidase / Peroxidase / Peroxidases proximal heme-ligand signature. / Haem peroxidase superfamily 類似検索 - ドメイン・相同性
ジャーナル: Structure / 年: 2021 タイトル: Using cryo-EM to understand antimycobacterial resistance in the catalase-peroxidase (KatG) from Mycobacterium tuberculosis. 著者: Asma Munir / Michael T Wilson / Steven W Hardwick / Dimitri Y Chirgadze / Jonathan A R Worrall / Tom L Blundell / Amanda K Chaplin / 要旨: 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 ...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.