Cryo-EM structure of hybrid respiratory supercomplex consisting of Mycobacterium tuberculosis complexIII and Mycobacterium smegmatis complexIV in presence of TB47
マップデータ
試料
複合体: hybrid respiratory supercomplex consisting of Mycobacterium tuberculosis complexIII and Mycobacterium smegmatis complexIV in presence of TB47
複合体: Mycobacterium smegmatis
タンパク質・ペプチド: x 7種
複合体: Mycobacterium tuberculosis complexIII
タンパク質・ペプチド: x 3種
リガンド: x 11種
キーワード
Mycobacterium smegmatis / mycobacterium tuberculosis / complexIII / complexIV / electron transport / anti-TB drugs / OXIDOREDUCTASE
機能・相同性
機能・相同性情報
aerobic electron transport chain / cytochrome-c oxidase / quinol-cytochrome-c reductase / quinol-cytochrome-c reductase activity / cytochrome-c oxidase activity / oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen / ATP synthesis coupled electron transport / peptidoglycan-based cell wall / respiratory electron transport chain / monooxygenase activity ...aerobic electron transport chain / cytochrome-c oxidase / quinol-cytochrome-c reductase / quinol-cytochrome-c reductase activity / cytochrome-c oxidase activity / oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen / ATP synthesis coupled electron transport / peptidoglycan-based cell wall / respiratory electron transport chain / monooxygenase activity / electron transport chain / 2 iron, 2 sulfur cluster binding / oxidoreductase activity / iron ion binding / copper ion binding / heme binding / metal ion binding / membrane / plasma membrane 類似検索 - 分子機能
Protein of unknown function DUF5130 / Domain of unknown function (DUF5130) / Cytochrome bc1 complex, cytochrome c subunit / Cytochrome c oxidase subunit IV, actinobacteria / QcrA subunit, N-terminal / Cytochrome c oxidase subunit IV / QcrA subunit N-terminal region / Cytochrome b(N-terminal)/b6/petB / : / Cytochrome C oxidase, cbb3-type, subunit III ...Protein of unknown function DUF5130 / Domain of unknown function (DUF5130) / Cytochrome bc1 complex, cytochrome c subunit / Cytochrome c oxidase subunit IV, actinobacteria / QcrA subunit, N-terminal / Cytochrome c oxidase subunit IV / QcrA subunit N-terminal region / Cytochrome b(N-terminal)/b6/petB / : / Cytochrome C oxidase, cbb3-type, subunit III / Cytochrome c oxidase subunit III / Cytochrome c oxidase subunit III-like / Cytochrome c oxidase, subunit III, 4-helical bundle / Cytochrome c oxidase subunit III / Heme-copper oxidase subunit III family profile. / Cytochrome c oxidase subunit III-like superfamily / Cytochrome c/quinol oxidase subunit II / Copper centre Cu(A) / CO II and nitrous oxide reductase dinuclear copper centers signature. / Cytochrome C oxidase subunit II, transmembrane domain superfamily / Cytochrome C oxidase subunit II, periplasmic domain / Cytochrome c oxidase subunit II-like C-terminal / Cytochrome oxidase subunit II copper A binding domain profile. / Cytochrome b/b6, N-terminal / Cytochrome b/b6-like domain superfamily / Cytochrome b/b6 N-terminal region profile. / Di-haem cytochrome, transmembrane / Rieske iron-sulphur protein / Cytochrome c / Rieske [2Fe-2S] domain / Rieske [2Fe-2S] iron-sulphur domain / Rieske [2Fe-2S] iron-sulfur domain profile. / Rieske [2Fe-2S] iron-sulphur domain superfamily / Cytochrome c family profile. / Cytochrome c-like domain / Cytochrome c-like domain superfamily / Cupredoxin / Prokaryotic membrane lipoprotein lipid attachment site profile. 類似検索 - ドメイン・相同性
Probable cytochrome c oxidase subunit 3 / Cytochrome c oxidase polypeptide 4 / cytochrome-c oxidase / Uncharacterized protein MSMEG_4692/MSMEI_4575 / Uncharacterized protein / Cytochrome bc1 complex Rieske iron-sulfur subunit / Cytochrome bc1 complex cytochrome c subunit / Cytochrome bc1 complex cytochrome b subunit 類似検索 - 構成要素
National Natural Science Foundation of China (NSFC)
81520108019
中国
National Natural Science Foundation of China (NSFC)
813300237
中国
引用
ジャーナル: Elife / 年: 2021 タイトル: Structure of cytochrome in complex with Q203 and TB47, two anti-TB drug candidates. 著者: Shan Zhou / Weiwei Wang / Xiaoting Zhou / Yuying Zhang / Yuezheng Lai / Yanting Tang / Jinxu Xu / Dongmei Li / Jianping Lin / Xiaolin Yang / Ting Ran / Hongming Chen / Luke W Guddat / Quan ...著者: Shan Zhou / Weiwei Wang / Xiaoting Zhou / Yuying Zhang / Yuezheng Lai / Yanting Tang / Jinxu Xu / Dongmei Li / Jianping Lin / Xiaolin Yang / Ting Ran / Hongming Chen / Luke W Guddat / Quan Wang / Yan Gao / Zihe Rao / Hongri Gong / 要旨: Pathogenic mycobacteria pose a sustained threat to global human health. Recently, cytochrome complexes have gained interest as targets for antibiotic drug development. However, there is currently no ...Pathogenic mycobacteria pose a sustained threat to global human health. Recently, cytochrome complexes have gained interest as targets for antibiotic drug development. However, there is currently no structural information for the cytochrome complex from these pathogenic mycobacteria. Here, we report the structures of cytochrome alone (2.68 Å resolution) and in complex with clinical drug candidates Q203 (2.67 Å resolution) and TB47 (2.93 Å resolution) determined by single-particle cryo-electron microscopy. cytochrome forms a dimeric assembly with endogenous menaquinone/menaquinol bound at the quinone/quinol-binding pockets. We observe Q203 and TB47 bound at the quinol-binding site and stabilized by hydrogen bonds with the side chains of Thr and Glu, residues that are conserved across pathogenic mycobacteria. These high-resolution images provide a basis for the design of new mycobacterial cytochrome inhibitors that could be developed into broad-spectrum drugs to treat mycobacterial infections.