QCRB_MYCTU
ID QCRB_MYCTU Reviewed; 549 AA.
AC P9WP37; L0TAG7; P63885; Q10388;
DT 16-APR-2014, integrated into UniProtKB/Swiss-Prot.
DT 16-APR-2014, sequence version 1.
DT 03-AUG-2022, entry version 42.
DE RecName: Full=Cytochrome bc1 complex cytochrome b subunit;
DE EC=7.1.1.8 {ECO:0000305};
DE AltName: Full=Cytochrome bc1 reductase complex subunit QcrB;
DE AltName: Full=Ubiquinol--cytochrome c reductase cytochrome b subunit;
GN Name=qcrB; OrderedLocusNames=Rv2196; ORFNames=MTCY190.07;
OS Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv).
OC Bacteria; Actinobacteria; Corynebacteriales; Mycobacteriaceae;
OC Mycobacterium; Mycobacterium tuberculosis complex.
OX NCBI_TaxID=83332;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=9634230; DOI=10.1038/31159;
RA Cole S.T., Brosch R., Parkhill J., Garnier T., Churcher C.M., Harris D.E.,
RA Gordon S.V., Eiglmeier K., Gas S., Barry C.E. III, Tekaia F., Badcock K.,
RA Basham D., Brown D., Chillingworth T., Connor R., Davies R.M., Devlin K.,
RA Feltwell T., Gentles S., Hamlin N., Holroyd S., Hornsby T., Jagels K.,
RA Krogh A., McLean J., Moule S., Murphy L.D., Oliver S., Osborne J.,
RA Quail M.A., Rajandream M.A., Rogers J., Rutter S., Seeger K., Skelton S.,
RA Squares S., Squares R., Sulston J.E., Taylor K., Whitehead S.,
RA Barrell B.G.;
RT "Deciphering the biology of Mycobacterium tuberculosis from the complete
RT genome sequence.";
RL Nature 393:537-544(1998).
RN [2]
RP IDENTIFICATION AS A DRUG TARGET [LARGE SCALE ANALYSIS].
RX PubMed=19099550; DOI=10.1186/1752-0509-2-109;
RA Raman K., Yeturu K., Chandra N.;
RT "targetTB: a target identification pipeline for Mycobacterium tuberculosis
RT through an interactome, reactome and genome-scale structural analysis.";
RL BMC Syst. Biol. 2:109-109(2008).
RN [3]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=21969609; DOI=10.1074/mcp.m111.011627;
RA Kelkar D.S., Kumar D., Kumar P., Balakrishnan L., Muthusamy B., Yadav A.K.,
RA Shrivastava P., Marimuthu A., Anand S., Sundaram H., Kingsbury R.,
RA Harsha H.C., Nair B., Prasad T.S., Chauhan D.S., Katoch K., Katoch V.M.,
RA Kumar P., Chaerkady R., Ramachandran S., Dash D., Pandey A.;
RT "Proteogenomic analysis of Mycobacterium tuberculosis by high resolution
RT mass spectrometry.";
RL Mol. Cell. Proteomics 10:M111.011627-M111.011627(2011).
RN [4]
RP FUNCTION, ACTIVITY REGULATION, AND MUTAGENESIS OF THR-313.
RC STRAIN=H37Rv;
RX PubMed=23913123; DOI=10.1038/nm.3262;
RA Pethe K., Bifani P., Jang J., Kang S., Park S., Ahn S., Jiricek J.,
RA Jung J., Jeon H.K., Cechetto J., Christophe T., Lee H., Kempf M.,
RA Jackson M., Lenaerts A.J., Pham H., Jones V., Seo M.J., Kim Y.M., Seo M.,
RA Seo J.J., Park D., Ko Y., Choi I., Kim R., Kim S.Y., Lim S., Yim S.A.,
RA Nam J., Kang H., Kwon H., Oh C.T., Cho Y., Jang Y., Kim J., Chua A.,
RA Tan B.H., Nanjundappa M.B., Rao S.P., Barnes W.S., Wintjens R.,
RA Walker J.R., Alonso S., Lee S., Kim J., Oh S., Oh T., Nehrbass U.,
RA Han S.J., No Z., Lee J., Brodin P., Cho S.N., Nam K., Kim J.;
RT "Discovery of Q203, a potent clinical candidate for the treatment of
RT tuberculosis.";
RL Nat. Med. 19:1157-1160(2013).
RN [5]
RP FUNCTION, ACTIVITY REGULATION, MUTAGENESIS OF LEU-176 AND THR-313, AND
RP 3D-STRUCTURE MODELING.
RC STRAIN=H37Rv;
RX PubMed=26158909; DOI=10.1038/ncomms8659;
RA Rybniker J., Vocat A., Sala C., Busso P., Pojer F., Benjak A., Cole S.T.;
RT "Lansoprazole is an antituberculous prodrug targeting cytochrome bc1.";
RL Nat. Commun. 6:7659-7659(2015).
CC -!- FUNCTION: Cytochrome b subunit of the cytochrome bc1 complex, an
CC essential component of the respiratory electron transport chain
CC required for ATP synthesis. The bc1 complex catalyzes the oxidation of
CC ubiquinol and the reduction of cytochrome c in the respiratory chain.
CC The bc1 complex operates through a Q-cycle mechanism that couples
CC electron transfer to generation of the proton gradient that drives ATP
CC synthesis. The cytochrome b subunit contains two ubiquinol reactive
CC sites: the oxidation (QP) site and the reduction (QN) site.
CC {ECO:0000305, ECO:0000305|PubMed:23913123,
CC ECO:0000305|PubMed:26158909}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a quinol + 2 Fe(III)-[cytochrome c](out) = a quinone + 2
CC Fe(II)-[cytochrome c](out) + 2 H(+)(out); Xref=Rhea:RHEA:11484,
CC Rhea:RHEA-COMP:10350, Rhea:RHEA-COMP:14399, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:24646, ChEBI:CHEBI:29033, ChEBI:CHEBI:29034,
CC ChEBI:CHEBI:132124; EC=7.1.1.8; Evidence={ECO:0000305};
CC -!- COFACTOR:
CC Name=heme; Xref=ChEBI:CHEBI:30413;
CC Evidence={ECO:0000250|UniProtKB:P00163};
CC Note=Binds 2 heme groups non-covalently per subunit.
CC {ECO:0000250|UniProtKB:P00163};
CC -!- ACTIVITY REGULATION: Inhibited by the anti-tuberculous drug Q203, an
CC optimized imidazopyridine amide (IPA) compound. Q203 triggers a rapid
CC ATP depletion in M.tuberculosis grown under an aerobic or anaerobic
CC atmosphere (PubMed:23913123). Also inhibited by LPZS (lansoprazole
CC sulfide), a metabolite of LPZ (lansoprazole) generated by intracellular
CC sulfoxide reduction into the host cytoplasm; LPZS is a potent anti-
CC mycobacterial agent that inhibits growth of intracellular
CC M.tuberculosis with good activity against drug-resistant isolates. The
CC inhibition of QcrB by LPZS leads to disruption of the mycobacterial
CC respiratory chain and massive and rapid ATP depletion
CC (PubMed:26158909). Both compounds target the same active site in QcrB
CC (the ubiquinol oxidation QP site), but they have distinct drug-binding
CC mechanisms (PubMed:26158909). {ECO:0000269|PubMed:23913123,
CC ECO:0000269|PubMed:26158909}.
CC -!- SUBUNIT: The cytochrome bc1 complex is composed of a cytochrome b
CC (QcrB), the Rieske iron-sulfur protein (QcrA) and a diheme cytochrome c
CC (QcrC) subunit. {ECO:0000305}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000255}; Multi-pass membrane
CC protein {ECO:0000255}.
CC -!- MISCELLANEOUS: Was identified as a high-confidence drug target.
CC {ECO:0000303|PubMed:19099550}.
CC -!- SIMILARITY: Belongs to the cytochrome b family. {ECO:0000255|PROSITE-
CC ProRule:PRU00968}.
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DR EMBL; AL123456; CCP44973.1; -; Genomic_DNA.
DR PIR; E70784; E70784.
DR RefSeq; NP_216712.1; NC_000962.3.
DR RefSeq; WP_003899212.1; NZ_NVQJ01000008.1.
DR PDB; 7E1V; EM; 2.68 A; B/N=1-549.
DR PDB; 7E1W; EM; 2.67 A; B/N=1-549.
DR PDB; 7E1X; EM; 2.93 A; B/N=1-549.
DR PDBsum; 7E1V; -.
DR PDBsum; 7E1W; -.
DR PDBsum; 7E1X; -.
DR AlphaFoldDB; P9WP37; -.
DR SMR; P9WP37; -.
DR STRING; 83332.Rv2196; -.
DR ChEMBL; CHEMBL4295794; -.
DR PaxDb; P9WP37; -.
DR DNASU; 887400; -.
DR GeneID; 45426172; -.
DR GeneID; 887400; -.
DR KEGG; mtu:Rv2196; -.
DR TubercuList; Rv2196; -.
DR eggNOG; COG1290; Bacteria.
DR OMA; WNYGPYD; -.
DR PhylomeDB; P9WP37; -.
DR Proteomes; UP000001584; Chromosome.
DR GO; GO:0005887; C:integral component of plasma membrane; HDA:MTBBASE.
DR GO; GO:0005886; C:plasma membrane; HDA:MTBBASE.
DR GO; GO:0070469; C:respirasome; IEA:UniProtKB-KW.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0008121; F:ubiquinol-cytochrome-c reductase activity; IEA:UniProtKB-EC.
DR GO; GO:0022904; P:respiratory electron transport chain; IEA:InterPro.
DR Gene3D; 1.20.810.10; -; 1.
DR InterPro; IPR005797; Cyt_b/b6_N.
DR InterPro; IPR027387; Cytb/b6-like_sf.
DR InterPro; IPR016174; Di-haem_cyt_TM.
DR Pfam; PF13631; Cytochrom_B_N_2; 1.
DR SUPFAM; SSF81342; SSF81342; 1.
DR PROSITE; PS51002; CYTB_NTER; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cell membrane; Electron transport; Heme; Iron; Membrane;
KW Metal-binding; Reference proteome; Respiratory chain; Translocase;
KW Transmembrane; Transmembrane helix; Transport.
FT CHAIN 1..549
FT /note="Cytochrome bc1 complex cytochrome b subunit"
FT /id="PRO_0000061927"
FT TRANSMEM 45..65
FT /note="Helical"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00968"
FT TRANSMEM 118..138
FT /note="Helical"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00968"
FT TRANSMEM 146..166
FT /note="Helical"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00968"
FT TRANSMEM 189..209
FT /note="Helical"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00968"
FT TRANSMEM 217..237
FT /note="Helical"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00968"
FT TRANSMEM 266..286
FT /note="Helical"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00968"
FT TRANSMEM 335..355
FT /note="Helical"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00968"
FT TRANSMEM 381..401
FT /note="Helical"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00968"
FT TRANSMEM 418..438
FT /note="Helical"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00968"
FT BINDING 114
FT /ligand="heme"
FT /ligand_id="ChEBI:CHEBI:30413"
FT /ligand_label="1"
FT /ligand_part="Fe"
FT /ligand_part_id="ChEBI:CHEBI:18248"
FT /note="axial binding residue"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00968"
FT BINDING 128
FT /ligand="heme"
FT /ligand_id="ChEBI:CHEBI:30413"
FT /ligand_label="2"
FT /ligand_part="Fe"
FT /ligand_part_id="ChEBI:CHEBI:18248"
FT /note="axial binding residue"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00968"
FT BINDING 216
FT /ligand="heme"
FT /ligand_id="ChEBI:CHEBI:30413"
FT /ligand_label="1"
FT /ligand_part="Fe"
FT /ligand_part_id="ChEBI:CHEBI:18248"
FT /note="axial binding residue"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00968"
FT BINDING 231
FT /ligand="heme"
FT /ligand_id="ChEBI:CHEBI:30413"
FT /ligand_label="2"
FT /ligand_part="Fe"
FT /ligand_part_id="ChEBI:CHEBI:18248"
FT /note="axial binding residue"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00968"
FT MUTAGEN 176
FT /note="L->P: Confers resistance to LPZS. Remains
FT susceptible to IPA."
FT /evidence="ECO:0000269|PubMed:26158909"
FT MUTAGEN 313
FT /note="T->A: Confers resistance to Q203 and IPA. Remains
FT susceptible to LPZS."
FT /evidence="ECO:0000269|PubMed:23913123,
FT ECO:0000269|PubMed:26158909"
FT HELIX 15..25
FT /evidence="ECO:0007829|PDB:7E1W"
FT HELIX 30..35
FT /evidence="ECO:0007829|PDB:7E1W"
FT HELIX 43..46
FT /evidence="ECO:0007829|PDB:7E1W"
FT HELIX 47..65
FT /evidence="ECO:0007829|PDB:7E1W"
FT TURN 66..68
FT /evidence="ECO:0007829|PDB:7E1W"
FT STRAND 75..77
FT /evidence="ECO:0007829|PDB:7E1W"
FT HELIX 83..85
FT /evidence="ECO:0007829|PDB:7E1W"
FT STRAND 89..91
FT /evidence="ECO:0007829|PDB:7E1W"
FT HELIX 92..103
FT /evidence="ECO:0007829|PDB:7E1W"
FT HELIX 107..135
FT /evidence="ECO:0007829|PDB:7E1W"
FT TURN 136..138
FT /evidence="ECO:0007829|PDB:7E1W"
FT HELIX 140..142
FT /evidence="ECO:0007829|PDB:7E1W"
FT HELIX 143..164
FT /evidence="ECO:0007829|PDB:7E1W"
FT HELIX 170..184
FT /evidence="ECO:0007829|PDB:7E1W"
FT STRAND 187..190
FT /evidence="ECO:0007829|PDB:7E1W"
FT HELIX 192..199
FT /evidence="ECO:0007829|PDB:7E1W"
FT STRAND 200..204
FT /evidence="ECO:0007829|PDB:7E1W"
FT HELIX 208..217
FT /evidence="ECO:0007829|PDB:7E1W"
FT HELIX 219..237
FT /evidence="ECO:0007829|PDB:7E1W"
FT STRAND 254..257
FT /evidence="ECO:0007829|PDB:7E1W"
FT HELIX 258..283
FT /evidence="ECO:0007829|PDB:7E1W"
FT TURN 289..291
FT /evidence="ECO:0007829|PDB:7E1W"
FT TURN 308..310
FT /evidence="ECO:0007829|PDB:7E1W"
FT HELIX 311..318
FT /evidence="ECO:0007829|PDB:7E1W"
FT STRAND 325..327
FT /evidence="ECO:0007829|PDB:7E1V"
FT STRAND 330..332
FT /evidence="ECO:0007829|PDB:7E1V"
FT HELIX 335..348
FT /evidence="ECO:0007829|PDB:7E1W"
FT TURN 349..351
FT /evidence="ECO:0007829|PDB:7E1W"
FT HELIX 352..360
FT /evidence="ECO:0007829|PDB:7E1W"
FT TURN 372..374
FT /evidence="ECO:0007829|PDB:7E1W"
FT HELIX 376..394
FT /evidence="ECO:0007829|PDB:7E1W"
FT HELIX 398..404
FT /evidence="ECO:0007829|PDB:7E1W"
FT HELIX 409..447
FT /evidence="ECO:0007829|PDB:7E1W"
FT STRAND 454..456
FT /evidence="ECO:0007829|PDB:7E1W"
FT TURN 458..461
FT /evidence="ECO:0007829|PDB:7E1W"
FT TURN 493..495
FT /evidence="ECO:0007829|PDB:7E1W"
FT STRAND 496..499
FT /evidence="ECO:0007829|PDB:7E1W"
FT STRAND 505..509
FT /evidence="ECO:0007829|PDB:7E1W"
FT HELIX 513..536
FT /evidence="ECO:0007829|PDB:7E1W"
SQ SEQUENCE 549 AA; 61014 MW; 0E75E0BCAA46B3A7 CRC64;
MSPKLSPPNI GEVLARQAED IDTRYHPSAA LRRQLNKVFP THWSFLLGEI ALYSFVVLLI
TGVYLTLFFD PSMVDVTYNG VYQPLRGVEM SRAYQSALDI SFEVRGGLFV RQIHHWAALM
FAAAIMVHLA RIFFTGAFRR PRETNWVIGS LLLILAMFEG YFGYSLPDDL LSGLGLRAAL
SSITLGMPVI GTWLHWALFG GDFPGTILIP RLYALHILLL PGIILALIGL HLALVWFQKH
TQFPGPGRTE HNVVGVRVMP VFAFKSGAFF AAIVGVLGLM GGLLQINPIW NLGPYKPSQV
SAGSQPDFYM MWTEGLARIW PPWEFYFWHH TIPAPVWVAV IMGLVFVLLP AYPFLEKRFT
GDYAHHNLLQ RPRDVPVRTA IGAMAIAFYM VLTLAAMNDI IALKFHISLN ATTWIGRIGM
VILPPFVYFI TYRWCIGLQR SDRSVLEHGV ETGIIKRLPH GAYIELHQPL GPVDEHGHPI
PLQYQGAPLP KRMNKLGSAG SPGSGSFLFA DSAAEDAALR EAGHAAEQRA LAALREHQDS
IMGSPDGEH
