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| - | [[Image:Secondary Structure of inhA.png|thumb|left| | + | [[Image:Secondary Structure of inhA.png|thumb|left|Width200Height300|alt=Secondary Structure Succession of inhA. Secondary structure residues are ordered from blue to red.|Secondary structure succession inhA.]] |
Revision as of 16:02, 31 March 2011
| This Sandbox is Reserved from January 10, 2010, through April 10, 2011 for use in BCMB 307-Proteins course taught by Andrea Gorrell at the University of Northern British Columbia, Prince George, BC, Canada. |
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InhA
by Kelly Hrywkiw
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| 2h9i, resolution 2.20Å () | |||||||||
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| 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 | ||||||||
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| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||||
Contents |
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 of inhA
The overall strucuture of the inhA enzyme of Mycobacterium tuberculosis consists of a single domain with two substructures that are connected by short loop[1].
Substructure 1 of inhA
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consists of 6 parallel β strands and 4 α helices interwoven together to form a core α/β structure that contains the n-terminal domain[1]. The first substructure can be further broken down into two sections, the consisting of two β strands and two short α helicies [1]. The first section is connected to the by a β strand that crosses over the two domains, and leads into the second section initiating at the third α helix [1]. (A-3) is connected by a long loop to a 14 residue β strand that then leads into the fourth α helix [1]. A-4 then leads into a fifth strand β , followed by a 25 residue α helix , and into the final strand β [1].
Substructure 2 of inhA
contains the c-terminal region of the molecule and consists of a small β strand (B-7), and two α helicies (A-6 and A-7) which are conected by a short five residue loop[1].
Physiological Function
Role in the Mycolic Acid Pathway
Protein Superfamilly
References
- ↑ 1.0 1.1 1.2 1.3 1.4 1.5 1.6 1.7 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
- ↑ 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
- ↑ 3.0 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
- ↑ . PMID:216315890657
