INHA_MYCBO
ID INHA_MYCBO Reviewed; 269 AA.
AC P0A5Y7; A0A1R3Y0K6; P46533; X2BIC8;
DT 15-MAR-2005, integrated into UniProtKB/Swiss-Prot.
DT 15-MAR-2005, sequence version 1.
DT 03-AUG-2022, entry version 106.
DE RecName: Full=Enoyl-[acyl-carrier-protein] reductase [NADH] {ECO:0000250|UniProtKB:P9WGR1};
DE Short=ENR {ECO:0000250|UniProtKB:P9WGR1};
DE Short=Enoyl-ACP reductase {ECO:0000250|UniProtKB:P9WGR1};
DE EC=1.3.1.9 {ECO:0000250|UniProtKB:P9WGR1};
DE AltName: Full=FAS-II enoyl-ACP reductase {ECO:0000250|UniProtKB:P9WGR1};
DE AltName: Full=NADH-dependent 2-trans-enoyl-ACP reductase {ECO:0000250|UniProtKB:P9WGR1};
GN Name=inhA {ECO:0000303|PubMed:8284673}; OrderedLocusNames=BQ2027_MB1520;
OS Mycobacterium bovis (strain ATCC BAA-935 / AF2122/97).
OC Bacteria; Actinobacteria; Corynebacteriales; Mycobacteriaceae;
OC Mycobacterium; Mycobacterium tuberculosis complex.
OX NCBI_TaxID=233413;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], CHARACTERIZATION OF VARIANT SER-94, AND
RP DRUG RESISTANCE.
RC STRAIN=BCG;
RX PubMed=8284673; DOI=10.1126/science.8284673;
RA Banerjee A., Dubnau E., Quemard A., Balasubramanian V., Um K.S., Wilson T.,
RA Collins D., de Lisle G., Jacobs W.R. Jr.;
RT "inhA, a gene encoding a target for isoniazid and ethionamide in
RT Mycobacterium tuberculosis.";
RL Science 263:227-230(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=WAG201;
RX PubMed=7623658; DOI=10.1111/j.1365-2958.1995.tb02276.x;
RA Wilson T.M., de Lisle G.W., Collins D.M.;
RT "Effect of inhA and katG on isoniazid resistance and virulence of
RT Mycobacterium bovis.";
RL Mol. Microbiol. 15:1009-1015(1995).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC BAA-935 / AF2122/97;
RX PubMed=12788972; DOI=10.1073/pnas.1130426100;
RA Garnier T., Eiglmeier K., Camus J.-C., Medina N., Mansoor H., Pryor M.,
RA Duthoy S., Grondin S., Lacroix C., Monsempe C., Simon S., Harris B.,
RA Atkin R., Doggett J., Mayes R., Keating L., Wheeler P.R., Parkhill J.,
RA Barrell B.G., Cole S.T., Gordon S.V., Hewinson R.G.;
RT "The complete genome sequence of Mycobacterium bovis.";
RL Proc. Natl. Acad. Sci. U.S.A. 100:7877-7882(2003).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND GENOME REANNOTATION.
RC STRAIN=ATCC BAA-935 / AF2122/97;
RX PubMed=28385856; DOI=10.1128/genomea.00157-17;
RA Malone K.M., Farrell D., Stuber T.P., Schubert O.T., Aebersold R.,
RA Robbe-Austerman S., Gordon S.V.;
RT "Updated reference genome sequence and annotation of Mycobacterium bovis
RT AF2122/97.";
RL Genome Announc. 5:E00157-E00157(2017).
RN [5]
RP DRUG TARGET, AND DRUG RESISTANCE.
RC STRAIN=BCG;
RX PubMed=12406221; DOI=10.1046/j.1365-2958.2002.03162.x;
RA Larsen M.H., Vilcheze C., Kremer L., Besra G.S., Parsons L., Salfinger M.,
RA Heifets L., Hazbon M.H., Alland D., Sacchettini J.C., Jacobs W.R. Jr.;
RT "Overexpression of inhA, but not kasA, confers resistance to isoniazid and
RT ethionamide in Mycobacterium smegmatis, M. bovis BCG and M. tuberculosis.";
RL Mol. Microbiol. 46:453-466(2002).
CC -!- FUNCTION: Enoyl-ACP reductase of the type II fatty acid syntase (FAS-
CC II) system, which is involved in the biosynthesis of mycolic acids, a
CC major component of mycobacterial cell walls. Catalyzes the NADH-
CC dependent reduction of the double bond of 2-trans-enoyl-[acyl-carrier
CC protein], an essential step in the fatty acid elongation cycle of the
CC FAS-II pathway. Shows preference for long-chain fatty acyl thioester
CC substrates, and can also use 2-trans-enoyl-CoAs as alternative
CC substrates. The mycobacterial FAS-II system utilizes the products of
CC the FAS-I system as primers to extend fatty acyl chain lengths up to
CC C56, forming the meromycolate chain that serves as the precursor for
CC final mycolic acids. {ECO:0000250|UniProtKB:P9WGR1}.
CC -!- FUNCTION: Is the primary target of the first-line antitubercular drug
CC isoniazid (INH) and of the second-line drug ethionamide (ETH)
CC (PubMed:12406221). Overexpressed inhA confers INH and ETH resistance to
CC M.bovis (PubMed:12406221). The mechanism of isoniazid action against
CC InhA is covalent attachment of the activated form of the drug to the
CC nicotinamide ring of NAD and binding of the INH-NAD adduct to the
CC active site of InhA (By similarity). Similarly, the ETH-NAD adduct
CC binds InhA (By similarity). {ECO:0000250|UniProtKB:P9WGR1,
CC ECO:0000269|PubMed:12406221}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 2,3-saturated acyl-[ACP] + NAD(+) = a (2E)-enoyl-[ACP] +
CC H(+) + NADH; Xref=Rhea:RHEA:10240, Rhea:RHEA-COMP:9925, Rhea:RHEA-
CC COMP:9926, ChEBI:CHEBI:15378, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945,
CC ChEBI:CHEBI:78784, ChEBI:CHEBI:78785; EC=1.3.1.9;
CC Evidence={ECO:0000250|UniProtKB:P9WGR1};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:10242;
CC Evidence={ECO:0000250|UniProtKB:P9WGR1};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 2,3-saturated acyl-CoA + NAD(+) = a (2E)-enoyl-CoA + H(+) +
CC NADH; Xref=Rhea:RHEA:18177, ChEBI:CHEBI:15378, ChEBI:CHEBI:57540,
CC ChEBI:CHEBI:57945, ChEBI:CHEBI:58856, ChEBI:CHEBI:65111;
CC Evidence={ECO:0000250|UniProtKB:P9WGR1};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:18179;
CC Evidence={ECO:0000250|UniProtKB:P9WGR1};
CC -!- PATHWAY: Lipid metabolism; mycolic acid biosynthesis.
CC {ECO:0000250|UniProtKB:P9WGR1}.
CC -!- SUBUNIT: Homodimer. Homotetramer. {ECO:0000250|UniProtKB:P9WGR1}.
CC -!- SIMILARITY: Belongs to the short-chain dehydrogenases/reductases (SDR)
CC family. FabI subfamily. {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; U41388; AAB60183.1; -; Genomic_DNA.
DR EMBL; LT708304; SIU00123.1; -; Genomic_DNA.
DR RefSeq; NP_855172.1; NC_002945.3.
DR RefSeq; WP_003407553.1; NC_002945.4.
DR AlphaFoldDB; P0A5Y7; -.
DR SMR; P0A5Y7; -.
DR EnsemblBacteria; SIU00123; SIU00123; BQ2027_MB1520.
DR GeneID; 45425463; -.
DR PATRIC; fig|233413.5.peg.1661; -.
DR OMA; GILDMIH; -.
DR UniPathway; UPA00915; -.
DR Proteomes; UP000001419; Chromosome.
DR GO; GO:0004318; F:enoyl-[acyl-carrier-protein] reductase (NADH) activity; IEA:UniProtKB-EC.
DR GO; GO:0016631; F:enoyl-[acyl-carrier-protein] reductase activity; IEA:UniProtKB-EC.
DR GO; GO:0050343; F:trans-2-enoyl-CoA reductase (NAD+) activity; IEA:RHEA.
DR GO; GO:0006633; P:fatty acid biosynthetic process; IEA:UniProtKB-KW.
DR GO; GO:0046677; P:response to antibiotic; IEA:UniProtKB-KW.
DR CDD; cd05372; ENR_SDR; 1.
DR InterPro; IPR014358; Enoyl-ACP_Rdtase_NADH.
DR InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR PANTHER; PTHR43159; PTHR43159; 1.
DR PIRSF; PIRSF000094; Enoyl-ACP_rdct; 1.
DR SUPFAM; SSF51735; SSF51735; 1.
PE 1: Evidence at protein level;
KW Antibiotic resistance; Fatty acid biosynthesis; Fatty acid metabolism;
KW Lipid biosynthesis; Lipid metabolism; NAD; Oxidoreductase.
FT CHAIN 1..269
FT /note="Enoyl-[acyl-carrier-protein] reductase [NADH]"
FT /id="PRO_0000054915"
FT BINDING 20..21
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:P9WGR1"
FT BINDING 64..65
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:P9WGR1"
FT BINDING 95..96
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:P9WGR1"
FT BINDING 158
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P9WGR1"
FT BINDING 165
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:P9WGR1"
FT BINDING 194
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:P9WGR1"
FT SITE 149
FT /note="May act as an intermediate that passes the hydride
FT ion from NADH to the substrate"
FT /evidence="ECO:0000250|UniProtKB:P9WGR1"
FT SITE 158
FT /note="Transition state stabilizer"
FT /evidence="ECO:0000250|UniProtKB:P9WGR1"
FT VARIANT 94
FT /note="S -> A (in strain: NZ; INH-resistant)"
FT /evidence="ECO:0000269|PubMed:8284673"
SQ SEQUENCE 269 AA; 28528 MW; F161D6D6A631CA08 CRC64;
MTGLLDGKRI LVSGIITDSS IAFHIARVAQ EQGAQLVLTG FDRLRLIQRI TDRLPAKAPL
LELDVQNEEH LASLAGRVTE AIGAGNKLDG VVHSIGFMPQ TGMGINPFFD APYADVSKGI
HISAYSYASM AKALLPIMNP GGSIVGMDFD PSRAMPAYNW MTVAKSALES VNRFVAREAG
KYGVRSNLVA AGPIRTLAMS AIVGGALGEE AGAQIQLLEE GWDQRAPIGW NMKDATPVAK
TVCALLSDWL PATTGDIIYA DGGAHTQLL
