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

UniProt P9WGR1 Organism Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv) Gene Rv1484, inhA EC 1.3.1.9

Also known as: Rv1484, inhA

Function

Enoyl-ACP reductase of the type II fatty acid syntase (FAS-II) system, which is involved in the biosynthesis of mycolic acids, a major component of mycobacterial cell walls. Catalyzes the NADH-dependent reduction of the double bond of 2-trans-enoyl-[acyl-carrier protein], an essential step in the fatty acid elongation cycle of the FAS-II pathway. Shows preference for long-chain fatty acyl thioester substrates (>C16), and can also use 2-trans-enoyl-CoAs as alternative substrates. The mycobacterial FAS-II system utilizes the products of the FAS-I system as primers to extend fatty acyl chain lengths up to C56, forming the meromycolate chain that serves as the precursor for final mycolic acids.

Classification

Family (Pfam): PF13561 adh_short_C2
InterPro: Enoyl-ACP_Rdtase_NADH, Mycobact_enoyl-ACP_red, NAD(P)-bd_dom_sf, SDR_fam
Functional cluster: RuBisCO & Carbon-Fixation Enzymes

Experimental structures · PDB · 117

1BVR X-ray 2.80A
1ENY X-ray 2.20A
1ENZ X-ray 2.70A
1P44 X-ray 2.70A
1P45 X-ray 2.60A
1ZID X-ray 2.70A
2AQ8 X-ray 1.92A
2AQH X-ray 2.01A
2AQI X-ray 2.20A
2AQK X-ray 2.30A
2B35 X-ray 2.30A
2B36 X-ray 2.80A
… and 105 more

A predicted model is available from AlphaFold.

Gene Ontology · 9

Drugs targeting this protein · 2

ETHIONAMIDE inhibitor
ISONIAZID inhibitor

Related proteins · sequence + function similarity

Co-cited proteins · studied together in the literature

Enoyl-[acyl-carrier-protein] reductase [NADH] 3 shared papers
Enoyl-[acyl-carrier-protein] reductase [NADH] 2 shared papers
Enoyl-[acyl-carrier-protein] reductase [NADH] 1 shared papers

Literature · 36 cited papers

Antitubercular drugs for an old target: GSK693 as a promising InhA direct inhibitor. EBioMedicine · 2016
N-Benzyl-4-((heteroaryl)methyl)benzamides: a new class of direct NADH-dependent 2-trans enoyl-acyl carrier protein reductase (InhA) inhibitors with antitubercular activity. ChemMedChem · 2016
Rational modulation of the induced-fit conformational change for slow-onset inhibition in Mycobacterium tuberculosis InhA. Biochemistry · 2015
Crystal structure of the enoyl-ACP reductase of Mycobacterium tuberculosis (InhA) in the apo-form and in complex with the active metabolite of isoniazid pre-formed by a biomimetic approach. J. Struct. Biol. · 2015
Direct inhibitors of InhA are active against Mycobacterium tuberculosis. Sci. Transl. Med. · 2015
Crucial components of Mycobacterium type II fatty acid biosynthesis (Fas-II) and their inhibitors. FEMS Microbiol. Lett. · 2014
Time-dependent diaryl ether inhibitors of InhA: structure-activity relationship studies of enzyme inhibition, antibacterial activity, and in vivo efficacy. ChemMedChem · 2014
A structural and energetic model for the slow-onset inhibition of the Mycobacterium tuberculosis enoyl-ACP reductase InhA. ACS Chem. Biol. · 2014
Pyridomycin bridges the NADH- and substrate-binding pockets of the enoyl reductase InhA. Nat. Chem. Biol. · 2014
Methyl-thiazoles: a novel mode of inhibition with the potential to develop novel inhibitors targeting InhA in Mycobacterium tuberculosis. J. Med. Chem. · 2013
Towards a new tuberculosis drug: pyridomycin - nature's isoniazid. EMBO Mol. Med. · 2012
Targeting InhA, the FASII enoyl-ACP reductase: SAR studies on novel inhibitor scaffolds. Curr. Top. Med. Chem. · 2012
… and 24 more in the literature graph

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