P0A5Y6 (INHA_MYCTU) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Enoyl-[acyl-carrier-protein] reductase [NADH]
EC=1.3.1.9

Alternative name(s):
NADH-dependent enoyl-ACP reductase

Gene names

Name:	inhA
Ordered Locus Names:	Rv1484, MT1531
ORF Names:	MTCY277.05

Organism

Mycobacterium tuberculosis

Taxonomic identifier

1773 [NCBI]

Taxonomic lineage

Bacteria › Actinobacteria › Actinobacteridae › Actinomycetales › Corynebacterineae › Mycobacteriaceae › Mycobacterium › Mycobacterium tuberculosis complex

Protein attributes

Sequence length	269 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Catalytic activity	Acyl-[acyl-carrier-protein] + NAD+ = trans-2,3-dehydroacyl-[acyl-carrier-protein] + NADH.
Pathway	Lipid metabolism; fatty acid biosynthesis.
Subunit structure	Homotetramer.
Miscellaneous	Target of the preferred antitubercular drug isoniazid (INH) which specifically inhibits inhA by covalent attachment of the activated form of the drug to the nicotinamide ring of nicotinamide adenine dinucleotide bound within the active site of the enzyme. Involved in the resistance against both isoniazid and ethionamide (ETH). Was identified as a high-confidence drug target.
Sequence similarities	Belongs to the short-chain dehydrogenases/reductases (SDR) family. FabI subfamily.

Ontologies

Keywords
Biological process	Antibiotic resistance Fatty acid biosynthesis Lipid synthesis
Ligand	NAD
Molecular function	Oxidoreductase
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	fatty acid elongation Inferred from mutant phenotype. Source: MTBBASE mycolic acid biosynthetic process Inferred from direct assay. Source: MTBBASE response to antibiotic Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	plasma membrane Inferred from direct assay. Source: MTBBASE
Molecular function	NAD+ binding Inferred from direct assay Ref.7. Source: MTBBASE enoyl-[acyl-carrier-protein] reductase (NADH) activity Inferred from direct assay. Source: MTBBASE fatty acid binding Inferred from direct assay Ref.7. Source: MTBBASE
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 269

269

Enoyl-[acyl-carrier-protein] reductase [NADH]

PRO_0000054916

Regions

Nucleotide binding

136 – 165

30

NAD Potential

Sites

Binding site

158

1

Substrate

Natural variations

Natural variant

94

1

S → A in strain: NZ; INH-resistant.

Secondary structure

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269

Helix Strand Turn

Details...

Turn

4 – 7

4

Beta strand

9 – 13

5

Helix

21 – 31

11

Beta strand

35 – 40

6

Helix

44 – 51

8

Beta strand

54 – 56

3

Beta strand

60 – 62

3

Helix

68 – 72

5

Helix

74 – 82

9

Beta strand

88 – 93

6

Helix

100 – 102

3

Beta strand

104 – 106

3

Helix

108 – 110

3

Helix

113 – 123

11

Helix

125 – 134

10

Helix

135 – 137

3

Beta strand

138 – 148

11

Beta strand

152 – 154

3

Helix

159 – 180

22

Turn

181 – 183

3

Beta strand

185 – 191

7

Helix

197 – 203

7

Turn

204 – 207

4

Helix

209 – 225

17

Helix

236 – 246

11

Beta strand

255 – 261

7

Helix

264 – 266

3

Sequences

	Sequence		Length	Mass (Da)
	P0A5Y6 [UniParc]. Last modified March 15, 2005. Version 1. Checksum: F161D6D6A631CA08	FASTA	269	28,528
	10 20 30 40 50 60 MTGLLDGKRI LVSGIITDSS IAFHIARVAQ EQGAQLVLTG FDRLRLIQRI TDRLPAKAPL 70 80 90 100 110 120 LELDVQNEEH LASLAGRVTE AIGAGNKLDG VVHSIGFMPQ TGMGINPFFD APYADVSKGI 130 140 150 160 170 180 HISAYSYASM AKALLPIMNP GGSIVGMDFD PSRAMPAYNW MTVAKSALES VNRFVAREAG 190 200 210 220 230 240 KYGVRSNLVA AGPIRTLAMS AIVGGALGEE AGAQIQLLEE GWDQRAPIGW NMKDATPVAK 250 260 TVCALLSDWL PATTGDIIYA DGGAHTQLL

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"inhA, a gene encoding a target for isoniazid and ethionamide in Mycobacterium tuberculosis." Banerjee A., Dubnau E., Quemard A., Balasubramanian V., Um K.S., Wilson T., Collins D., de Lisle G., Jacobs W.R. Jr. Science 263:227-230(1994) [PubMed: 8284673] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Strain: ATCC 25618 / H37Rv.
[2]	"Deciphering the biology of Mycobacterium tuberculosis from the complete genome sequence." Cole S.T., Brosch R., Parkhill J., Garnier T., Churcher C.M., Harris D.E., Gordon S.V., Eiglmeier K., Gas S., Barry C.E. III, Tekaia F., Badcock K., Basham D., Brown D., Chillingworth T., Connor R., Davies R.M., Devlin K. , Feltwell T., Gentles S., Hamlin N., Holroyd S., Hornsby T., Jagels K., Krogh A., McLean J., Moule S., Murphy L.D., Oliver S., Osborne J., Quail M.A., Rajandream M.A., Rogers J., Rutter S., Seeger K., Skelton S., Squares S., Squares R., Sulston J.E., Taylor K., Whitehead S., Barrell B.G. Nature 393:537-544(1998) [PubMed: 9634230] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: ATCC 25618 / H37Rv.
[3]	"Whole-genome comparison of Mycobacterium tuberculosis clinical and laboratory strains." Fleischmann R.D., Alland D., Eisen J.A., Carpenter L., White O., Peterson J.D., DeBoy R.T., Dodson R.J., Gwinn M.L., Haft D.H., Hickey E.K., Kolonay J.F., Nelson W.C., Umayam L.A., Ermolaeva M.D., Salzberg S.L., Delcher A., Utterback T.R. , Weidman J.F., Khouri H.M., Gill J., Mikula A., Bishai W., Jacobs W.R. Jr., Venter J.C., Fraser C.M. J. Bacteriol. 184:5479-5490(2002) [PubMed: 12218036] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: CDC 1551 / Oshkosh.
[4]	"targetTB: a target identification pipeline for Mycobacterium tuberculosis through an interactome, reactome and genome-scale structural analysis." Raman K., Yeturu K., Chandra N. BMC Syst. Biol. 2:109-109(2008) [PubMed: 19099550] [Abstract] Cited for: IDENTIFICATION AS A DRUG TARGET [LARGE SCALE ANALYSIS].
[5]	"Crystal structure and function of the isoniazid target of Mycobacterium tuberculosis." Dessen A., Quemard A., Blanchard J.S., Jacobs W.R. Jr., Sacchettini J.C. Science 267:1638-1641(1995) [PubMed: 7886450] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS).
[6]	"Modification of the NADH of the isoniazid target (InhA) from Mycobacterium tuberculosis." Rozwarski D.A., Grant G.A., Barton D.H.R., Jacobs W.R. Jr., Sacchettini J.C. Science 279:98-102(1998) [PubMed: 9417034] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS).
[7]	"Crystal structure of the Mycobacterium tuberculosis enoyl-ACP reductase, InhA, in complex with NAD+ and a C16 fatty acyl substrate." Rozwarski D.A., Vilcheze C., Sugantino M., Bittman R., Sacchettini J.C. J. Biol. Chem. 274:15582-15589(1999) [PubMed: 10336454] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) IN COMPLEX WITH NAD AND SUBSTRATE.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

U02492 Unassigned DNA. Translation: AAC43210.1.
BX842576 Genomic DNA. Translation: CAB02034.1.
AE000516 Genomic DNA. Translation: AAK45796.1.

PIR

G70710.

RefSeq

NP_216000.1. NC_000962.2.
NP_335982.1. NC_002755.2.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1BVR	X-ray	2.80	A/B/C/D/E/F	2-269	[»]
1ENY	X-ray	2.20	A	3-269	[»]
1ENZ	X-ray	2.70	A	3-269	[»]
1P44	X-ray	2.70	A/B/C/D/E/F	1-269	[»]
1P45	X-ray	2.60	A/B	1-269	[»]
1ZID	X-ray	2.70	A	3-269	[»]
2AQ8	X-ray	1.92	A	1-269	[»]
2AQH	X-ray	2.01	A	1-269	[»]
2AQI	X-ray	2.20	A	1-269	[»]
2AQK	X-ray	2.30	A	1-269	[»]
2B35	X-ray	2.30	A/B/C/D/E/F	1-269	[»]
2B36	X-ray	2.80	A/B/C/D/E/F	1-269	[»]
2B37	X-ray	2.60	A/B/C/D/E/F	1-269	[»]
2H7I	X-ray	1.62	A	1-269	[»]
2H7L	X-ray	1.73	A	1-269	[»]
2H7M	X-ray	1.62	A	1-269	[»]
2H7N	X-ray	1.90	A	1-269	[»]
2H7P	X-ray	1.86	A	1-269	[»]
2H9I	X-ray	2.20	A	3-269	[»]
2IDZ	X-ray	2.00	A	2-269	[»]
2IE0	X-ray	2.20	A	2-269	[»]
2IEB	X-ray	2.20	A	2-269	[»]
2IED	X-ray	2.14	A/B/C/D	2-269	[»]
2NSD	X-ray	1.90	A/B	1-269	[»]
2NTJ	X-ray	2.50	A/B	3-269	[»]
2NV6	X-ray	1.90	A	3-269	[»]
2PR2	X-ray	2.50	A	1-269	[»]
2X22	X-ray	2.10	A/B	1-269	[»]
2X23	X-ray	1.81	A/B/E/G	1-269	[»]
3FNE	X-ray	1.98	A/B/C/D	1-269	[»]
3FNF	X-ray	2.30	A/B/C/D	1-269	[»]
3FNG	X-ray	1.97	A	1-269	[»]
3FNH	X-ray	2.80	A	1-269	[»]
3OEW	X-ray	2.20	A	1-269	[»]
3OEY	X-ray	2.00	A	1-269	[»]
3OF2	X-ray	2.00	A	1-269	[»]

ProteinModelPortal

P0A5Y6.

SMR

P0A5Y6. Positions 2-269.

ModBase

Search...

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

EnsemblBacteria

EBMYCT00000000975; EBMYCP00000000975; EBMYCG00000000975.
EBMYCT00000070225; EBMYCP00000068284; EBMYCG00000070220.

GeneID

886523.
924440.

GenomeReviews

Gene locus MT1531 in contig AE000516_GR.
Gene locus Rv1484 in contig AL123456_GR.

KEGG

mtc:MT1531.
mtu:Rv1484.

PATRIC

18125130. VBIMycTub22151_1680.

TIGR

MT1531.

Organism-specific databases

TubercuList

Rv1484.

Phylogenomic databases

GeneTree

EBGT00050000015205.

HOGENOM

HBG750976.

OMA

DCDVGSD.

PhylomeDB

P0A5Y6.

ProtClustDB

PRK07889.

Family and domain databases

InterPro

IPR014358. Enoyl-ACP_Rdtase_NADH.
IPR016040. NAD(P)-bd_dom.
[Graphical view]

Gene3D

G3DSA:3.40.50.720. NAD(P)-bd. 1 hit.

KO

K11611.

PIRSF

PIRSF000094. Enoyl-ACP_rdct. 1 hit.

ProtoNet

Search...

Other

BindingDB

P0A5Y6.

DrugBank

DB00609. Ethionamide.
DB00951. Isoniazid.

Entry information

Entry name

INHA_MYCTU

Accession

Primary (citable) accession number: P0A5Y6
Secondary accession number(s): P46533

Entry history

Integrated into UniProtKB/Swiss-Prot:	March 15, 2005
Last sequence update:	March 15, 2005
Last modified:	January 25, 2012
This is version 65 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Prokaryotic Protein Annotation Program