Molecular Target Synopsis
Overview
Domains and Structures
Drugs and Clinical Candidates
Druggability
Chemistry
Ligand Efficiency Plot
Pathways
Family Cladogram
Interaction Network
Gene Expression
Gene Copy Number Variation
RNAi
Mutations
Germline Genetics

inhA (P9WGR1) - Overview - Molecular Target Synopsis

Protein


inhA, Enoyl-[acyl-carrier-protein] reductase [NADH]
Enzyme Classification 1.3.1.9
UniProt P9WGR1

Also Known as INHA_MYCTU, inhA

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 (PubMed:25227413). 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 (PubMed:7599116). Shows preference for long-chain fatty acyl thioester substrates (>C16), and can also use 2-trans-enoyl-CoAs as alternative substrates (PubMed:7599116). 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 (PubMed:25227413)., Is the primary target of the first-line antitubercular drug isoniazid (INH) and of the second-line drug ethionamide (ETH) (PubMed:8284673, PubMed:12406221, PubMed:16906155, PubMed:17227913). Overexpressed inhA confers INH and ETH resistance to M.tuberculosis (PubMed:12406221). The mechanism of isoniazid action against InhA is covalent attachment of the activated form of the drug to the nicotinamide ring of NAD and binding of the INH-NAD adduct to the active site of InhA (PubMed:9417034, PubMed:16906155). Similarly, the ETH-NAD adduct binds InhA (PubMed:17227913). Homodimer (PubMed:7599116). Homotetramer (PubMed:10336454, PubMed:16647717).

6EP8
INHA Y158F MUTANT IN COMPLEX WITH NADH FROM MYCOBACTERIUM TUBERCULOSIS
RCSB/PDB
Inspect Structure
See all 3D Structures for inhA

Isoforms / Transcripts (Protein Coding)


Protein Length Ensembl Gene Ensembl Transcript Ensembl Protein Uniprot Isoform

Drugs


inhA is targeted by Approved Drugs Isoniazid, Ethionamide. (see details)
Isoniazid
Ethionamide

Sub-cellular localization


GO terms: inhA is active in the following subcellular-locations: cell wall, plasma membrane.



UniProt
GO terms

Gene Copy Number Variation


In COSMIC - Cell Lines Project inhA has gain in 0 cell-lines, loss in 0 cell-lines and no signal in 0 cell-lines. (see details)

RNA Interference


inhA was reported in the following RNAI studies:

Cell - Large Scale Profiling of Kinase Dependencies in Cancer Cell Lines, the highest RNAi cell lines are: . (see details)

3D Structures


For inhA there are:
93 structures (264 chains) solved
88 are solved in complex with at least one small molecule ligand
2 are solved with an approved drug

inhA is solved in complex with the approved drug(s):

TCL/TRICLOSAN (1P45_A, 1P45_B, 2B35_A, 2B35_B, 2B35_C, 2B35_D, 2B35_E, 2B35_F).

(see details)
Molecular Target 3D Synopsis

Screening and Chemistry


inhA has been screened with compounds ( bioactivities). (see details)