NDH_MYCTU
ID NDH_MYCTU Reviewed; 463 AA.
AC P95160; F2GI96; I6XZ55; Q7D7W7;
DT 02-JUN-2021, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-1997, sequence version 1.
DT 03-AUG-2022, entry version 150.
DE RecName: Full=Type II NADH:quinone oxidoreductase Ndh {ECO:0000305};
DE EC=1.6.5.9 {ECO:0000269|PubMed:15767566, ECO:0000269|PubMed:29522317};
DE AltName: Full=Type II NADH dehydrogenase Ndh {ECO:0000303|PubMed:25128581};
GN Name=ndh {ECO:0000303|PubMed:15767566};
GN OrderedLocusNames=Rv1854c {ECO:0000312|EMBL:CCP44620.1};
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 FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, AND SUBCELLULAR
RP LOCATION.
RC STRAIN=H37Rv;
RX PubMed=15767566; DOI=10.1073/pnas.0500469102;
RA Weinstein E.A., Yano T., Li L.S., Avarbock D., Avarbock A., Helm D.,
RA McColm A.A., Duncan K., Lonsdale J.T., Rubin H.;
RT "Inhibitors of type II NADH:menaquinone oxidoreductase represent a class of
RT antitubercular drugs.";
RL Proc. Natl. Acad. Sci. U.S.A. 102:4548-4553(2005).
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 DISRUPTION PHENOTYPE.
RC STRAIN=ATCC 27294 / TMC 102 / H37Rv;
RX PubMed=25128581; DOI=10.1016/j.gene.2014.08.024;
RA Awasthy D., Ambady A., Narayana A., Morayya S., Sharma U.;
RT "Roles of the two type II NADH dehydrogenases in the survival of
RT Mycobacterium tuberculosis in vitro.";
RL Gene 550:110-116(2014).
RN [5]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=29382761; DOI=10.1073/pnas.1721545115;
RA Vilcheze C., Weinrick B., Leung L.W., Jacobs W.R. Jr.;
RT "Plasticity of Mycobacterium tuberculosis NADH dehydrogenases and their
RT role in virulence.";
RL Proc. Natl. Acad. Sci. U.S.A. 115:1599-1604(2018).
RN [6]
RP FUNCTION, CATALYTIC ACTIVITY, AND ACTIVITY REGULATION.
RC STRAIN=ATCC 27294 / TMC 102 / H37Rv;
RX PubMed=29522317; DOI=10.1021/acsinfecdis.7b00275;
RA Murugesan D., Ray P.C., Bayliss T., Prosser G.A., Harrison J.R., Green K.,
RA Soares de Melo C., Feng T.S., Street L.J., Chibale K., Warner D.F.,
RA Mizrahi V., Epemolu O., Scullion P., Ellis L., Riley J., Shishikura Y.,
RA Ferguson L., Osuna-Cabello M., Read K.D., Green S.R., Lamprecht D.A.,
RA Finin P.M., Steyn A.J.C., Ioerger T.R., Sacchettini J., Rhee K.Y.,
RA Arora K., Barry C.E. III, Wyatt P.G., Boshoff H.I.M.;
RT "2-Mercapto-Quinazolinones as Inhibitors of Type II NADH Dehydrogenase and
RT Mycobacterium tuberculosis: Structure-Activity Relationships, Mechanism of
RT Action and Absorption, Distribution, Metabolism, and Excretion
RT Characterization.";
RL ACS Infect. Dis. 4:954-969(2018).
CC -!- FUNCTION: Alternative, nonproton pumping NADH:quinone oxidoreductase
CC that delivers electrons to the respiratory chain by oxidation of NADH
CC and reduction of quinones (PubMed:15767566, PubMed:29382761,
CC PubMed:29522317). Ndh is probably the main NADH dehydrogenase of
CC M.tuberculosis (PubMed:29382761). {ECO:0000269|PubMed:15767566,
CC ECO:0000269|PubMed:29382761, ECO:0000269|PubMed:29522317}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a quinone + H(+) + NADH = a quinol + NAD(+);
CC Xref=Rhea:RHEA:46160, ChEBI:CHEBI:15378, ChEBI:CHEBI:24646,
CC ChEBI:CHEBI:57540, ChEBI:CHEBI:57945, ChEBI:CHEBI:132124; EC=1.6.5.9;
CC Evidence={ECO:0000269|PubMed:15767566, ECO:0000269|PubMed:29522317};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a menaquinone + H(+) + NADH = a menaquinol + NAD(+);
CC Xref=Rhea:RHEA:29235, Rhea:RHEA-COMP:9537, Rhea:RHEA-COMP:9539,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:16374, ChEBI:CHEBI:18151,
CC ChEBI:CHEBI:57540, ChEBI:CHEBI:57945;
CC Evidence={ECO:0000269|PubMed:15767566};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a ubiquinone + H(+) + NADH = a ubiquinol + NAD(+);
CC Xref=Rhea:RHEA:23152, Rhea:RHEA-COMP:9565, Rhea:RHEA-COMP:9566,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:16389, ChEBI:CHEBI:17976,
CC ChEBI:CHEBI:57540, ChEBI:CHEBI:57945;
CC Evidence={ECO:0000269|PubMed:29522317};
CC -!- COFACTOR:
CC Name=FAD; Xref=ChEBI:CHEBI:57692;
CC Evidence={ECO:0000250|UniProtKB:Q2FZV7};
CC Note=Binds 1 FAD per subunit. {ECO:0000250|UniProtKB:Q2FZV7};
CC -!- ACTIVITY REGULATION: Inhibited by phenothiazine analogs
CC (PubMed:15767566). Inhibited by 2-mercapto-quinazolinones
CC (PubMed:29522317). Not inhibited by classic inhibitors of type I NADH
CC dehydrogenase, such as rotenone, piericidin A and pyridaben
CC (PubMed:15767566). {ECO:0000269|PubMed:15767566,
CC ECO:0000269|PubMed:29522317}.
CC -!- SUBCELLULAR LOCATION: Cell inner membrane
CC {ECO:0000269|PubMed:15767566}; Single-pass membrane protein
CC {ECO:0000255}.
CC -!- DISRUPTION PHENOTYPE: Deletion mutant is attenuated for growth and
CC virulence in mice (PubMed:29382761). Deletion of the gene alters the
CC NADH/NAD(+) ratio, suggesting that this enzyme has an important
CC function in maintaining the redox status of the cell (PubMed:29382761).
CC Mutant shows growth defects in vitro and is more susceptible to
CC oxidative stress reagents, but not to potential NADH dehydrogenase
CC inhibitors (PubMed:29382761). Was considered as an essential gene in
CC vitro, but later studies show that ndh is not essential individually
CC (PubMed:25128581, PubMed:29382761). The ndh-ndhA double knockout could
CC not be obtained, suggesting that at least one type II NADH
CC dehydrogenase is required for M.tuberculosis growth (PubMed:29382761).
CC {ECO:0000269|PubMed:25128581, ECO:0000269|PubMed:29382761}.
CC -!- SIMILARITY: Belongs to the NADH dehydrogenase family. {ECO:0000305}.
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DR EMBL; AL123456; CCP44620.1; -; Genomic_DNA.
DR RefSeq; NP_216370.1; NC_000962.3.
DR RefSeq; WP_003409317.1; NZ_NVQJ01000013.1.
DR AlphaFoldDB; P95160; -.
DR SMR; P95160; -.
DR STRING; 83332.Rv1854c; -.
DR PaxDb; P95160; -.
DR PRIDE; P95160; -.
DR DNASU; 885746; -.
DR GeneID; 885746; -.
DR KEGG; mtu:Rv1854c; -.
DR PATRIC; fig|83332.111.peg.2060; -.
DR TubercuList; Rv1854c; -.
DR eggNOG; COG1252; Bacteria.
DR OMA; ELMGEFI; -.
DR PhylomeDB; P95160; -.
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:0003955; F:NAD(P)H dehydrogenase (quinone) activity; IDA:MTBBASE.
DR GO; GO:0003954; F:NADH dehydrogenase activity; IEA:InterPro.
DR GO; GO:0019646; P:aerobic electron transport chain; IDA:MTBBASE.
DR GO; GO:0006116; P:NADH oxidation; IEA:InterPro.
DR InterPro; IPR036188; FAD/NAD-bd_sf.
DR InterPro; IPR023753; FAD/NAD-binding_dom.
DR InterPro; IPR045024; NDH-2.
DR PANTHER; PTHR43706; PTHR43706; 1.
DR Pfam; PF07992; Pyr_redox_2; 1.
DR SUPFAM; SSF51905; SSF51905; 1.
PE 1: Evidence at protein level;
KW Cell inner membrane; Cell membrane; FAD; Flavoprotein; Membrane; NAD;
KW Oxidoreductase; Reference proteome; Transmembrane; Transmembrane helix.
FT CHAIN 1..463
FT /note="Type II NADH:quinone oxidoreductase Ndh"
FT /id="PRO_0000452727"
FT TRANSMEM 387..407
FT /note="Helical"
FT /evidence="ECO:0000255"
FT ACT_SITE 184
FT /evidence="ECO:0000250|UniProtKB:Q2FZV7"
FT BINDING 21..25
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:Q2FZV7"
FT BINDING 89
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:Q2FZV7"
FT BINDING 322
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:Q2FZV7"
FT BINDING 333..334
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:Q2FZV7"
SQ SEQUENCE 463 AA; 49619 MW; 97D9D0CFF0B886C5 CRC64;
MSPQQEPTAQ PPRRHRVVII GSGFGGLNAA KKLKRADVDI KLIARTTHHL FQPLLYQVAT
GIISEGEIAP PTRVVLRKQR NVQVLLGNVT HIDLAGQCVV SELLGHTYQT PYDSLIVAAG
AGQSYFGNDH FAEFAPGMKS IDDALELRGR ILSAFEQAER SSDPERRAKL LTFTVVGAGP
TGVEMAGQIA ELAEHTLKGA FRHIDSTKAR VILLDAAPAV LPPMGAKLGQ RAAARLQKLG
VEIQLGAMVT DVDRNGITVK DSDGTVRRIE SACKVWSAGV SASRLGRDLA EQSRVELDRA
GRVQVLPDLS IPGYPNVFVV GDMAAVEGVP GVAQGAIQGA KYVASTIKAE LAGANPAERE
PFQYFDKGSM ATVSRFSAVA KIGPVEFSGF IAWLIWLVLH LAYLIGFKTK ITTLLSWTVT
FLSTRRGQLT ITDQQAFART RLEQLAELAA EAQGSAASAK VAS
