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InhA

by Kelly Hrywkiw

spinqualitylabelsall models PDB ID 2h9i Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image
2h9i, resolution 2.20Å ()
Ligands:
Gene:	inhA (Mycobacterium tuberculosis)
Activity:	[acyl-carrier-protein_reductase_(NADH) Enoyl-[acyl-carrier-protein] reductase (NADH)], with EC number 1.3.1.9
Related:	1zid
Structural annotation: Resources: InterPro : Ipr014358, Ipr002198 UniProt : P0A5Y6
Functional annotation: Biological process: lipid biosynthetic process response to antibiotic fatty acid biosynthetic process metabolic process Molecular function: enoyl-[acyl-carrier-protein reductase (NADH) activity] oxidoreductase activity
Evolutionary conservation: Toggle Conservation Colors: Rows = identical sequences: Further Information: Caveats, Explanation, Complete Results at ConSurfDB
Resources:	FirstGlance, OCA, PDBsum, RCSB
Coordinates:	save as pdb, mmCIF, xml

Contents 1 Introduction 2 Structure 3 Role in the Mycolic Acid Pathway 4 Physiological Function 5 Protein Superfamilly 6 References

Introduction

The enzyme inhA is coded from the inhA gene that is simillar in sequence to the Salmonella typhimuriumgene which plays a role in fatty acid biosynthesis ^[1]. Inha is an NADH dependent trans enoyl-acyl ACP carrier protein that plays a role in the sysnthesis of Mycolic Acid, and is part of a short-chain dehydrogenase/reductase family ^[2][3]. Mycolic acids are long chain fatty acids that are essential in cell wall formation of the human pathogen Mycobacterium tuberculosisas well as other mycobateria such as Mycobacterium leprae^[4]. Inha has been propsed as the target of the thionamide drugs, ethionamide (ETH) and isoniazid (INH), which have been used in treatment of mycobacterial infections ^[3].

Structure

The overall strucuture of the inhA enzyme of Mycobacterium tuberculosis consists of a single domain with two substructures^[1]. The can be further broken down into two sections consisting of two β strands and two short α helicies ^[1].

Role in the Mycolic Acid Pathway

Physiological Function

Protein Superfamilly

References

1. ↑ ^{1.0 1.1 1.2} Strohmaier K, Streissle G, Clemm de Noronha S. [On the determination of size of early summer meningoencephalitis]. Arch Gesamte Virusforsch. 1965;17(2):300-3. PMID:5882878
2. ↑ Wang F, Langley R, Gulten G, Dover LG, Besra GS, Jacobs WR Jr, Sacchettini JC. Mechanism of thioamide drug action against tuberculosis and leprosy. J Exp Med. 2007 Jan 22;204(1):73-8. Epub 2007 Jan 16. PMID:17227913 doi:10.1084/jem.20062100
3. ↑ ^{3.0 3.1} Molle V, Gulten G, Vilcheze C, Veyron-Churlet R, Zanella-Cleon I, Sacchettini JC, Jacobs WR Jr, Kremer L. Phosphorylation of InhA inhibits mycolic acid biosynthesis and growth of Mycobacterium tuberculosis. Mol Microbiol. 2010 Dec;78(6):1591-605. doi:, 10.1111/j.1365-2958.2010.07446.x. Epub 2010 Nov 9. PMID:21143326 doi:10.1111/j.1365-2958.2010.07446.x
4. ↑ . PMID:216315890657