Sandbox Reserved 321
From Proteopedia
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| - | '''InhA''' | + | ='''InhA'''= |
by Kelly Hrywkiw | by Kelly Hrywkiw | ||
| + | {{STRUCTURE_2h9i | PDB=2h9i | SCENE= }} | ||
| + | __TOC__ | ||
[[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.]] | [[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.]] | ||
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| - | {{STRUCTURE_2h9i | PDB=2h9i | SCENE= }} | ||
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==Introduction== | ==Introduction== | ||
The enzyme inhA is coded from the inhA gene that is simillar in sequence to the ''[http://en.wikipedia.org/wiki/Salmonella_typhimurium Salmonella typhimurium]''gene which plays a role in fatty acid biosynthesis <ref name ="making drugs for inhA">PMID:5882878</ref>. 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 <ref name ="mech of thioamide drug action">PMID:17227913</ref><ref name ="phosphorylation of inhA">PMID:21143326</ref>. Mycolic acids are long chain fatty acids that are essential in cell wall formation of the human pathogen ''[http://en.wikipedia.org/wiki/Mycobacterium_tuberculosis Mycobacterium tuberculosis]''as well as other mycobateria such as ''[http://en.wikipedia.org/wiki/Mycobacterium_leprae Mycobacterium leprae]''<ref name ="TB">PMID2568869:</ref>. 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 <ref name ="phosphorylation of inhA">PMID:21143326</ref>. | The enzyme inhA is coded from the inhA gene that is simillar in sequence to the ''[http://en.wikipedia.org/wiki/Salmonella_typhimurium Salmonella typhimurium]''gene which plays a role in fatty acid biosynthesis <ref name ="making drugs for inhA">PMID:5882878</ref>. 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 <ref name ="mech of thioamide drug action">PMID:17227913</ref><ref name ="phosphorylation of inhA">PMID:21143326</ref>. Mycolic acids are long chain fatty acids that are essential in cell wall formation of the human pathogen ''[http://en.wikipedia.org/wiki/Mycobacterium_tuberculosis Mycobacterium tuberculosis]''as well as other mycobateria such as ''[http://en.wikipedia.org/wiki/Mycobacterium_leprae Mycobacterium leprae]''<ref name ="TB">PMID2568869:</ref>. 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 <ref name ="phosphorylation of inhA">PMID:21143326</ref>. | ||
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==Structure of inhA== | ==Structure of inhA== | ||
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| + | <Structure load='2h9i' size='300' frame='true' align='left' caption='inhA' scene='Sandbox_Reserved_321/Structural_progresion/1' /> | ||
The overall strucuture of the inhA enzyme of ''[http://en.wikipedia.org/wiki/Mycobacterium_tuberculosis Mycobacterium tuberculosis]'' consists of a single domain with two substructures that are connected by short loop<ref name ="making drugs for inhA">PMID:5882878</ref>. | The overall strucuture of the inhA enzyme of ''[http://en.wikipedia.org/wiki/Mycobacterium_tuberculosis Mycobacterium tuberculosis]'' consists of a single domain with two substructures that are connected by short loop<ref name ="making drugs for inhA">PMID:5882878</ref>. | ||
===Substructure 1 of inhA=== | ===Substructure 1 of inhA=== | ||
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| - | <Structure load='inhA' size='300' frame='true' align='left' caption='inhA' scene='Sandbox_Reserved_321/Test/1'/> | ||
<scene name='Sandbox_Reserved_321/Substructure_1/1'>Substructure 1</scene> 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<ref name ="making drugs for inhA">PMID:5882878</ref>. | <scene name='Sandbox_Reserved_321/Substructure_1/1'>Substructure 1</scene> 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<ref name ="making drugs for inhA">PMID:5882878</ref>. | ||
The first substructure can be further broken down into two sections, the <scene name='Sandbox_Reserved_321/Substructure1section1/7'>first section</scene> consisting of two β strands <scene name='Sandbox_Reserved_321/B-1_and_b-2/4'>(B-1 and B-2)</scene>and two short α helicies <scene name='Sandbox_Reserved_321/A-1_and_a-2/2'>(A-1 and A-2)</scene><ref name ="making drugs for inhA">PMID:5882878</ref>. | The first substructure can be further broken down into two sections, the <scene name='Sandbox_Reserved_321/Substructure1section1/7'>first section</scene> consisting of two β strands <scene name='Sandbox_Reserved_321/B-1_and_b-2/4'>(B-1 and B-2)</scene>and two short α helicies <scene name='Sandbox_Reserved_321/A-1_and_a-2/2'>(A-1 and A-2)</scene><ref name ="making drugs for inhA">PMID:5882878</ref>. | ||
| - | The first section is connected to the <scene name='Sandbox_Reserved_321/Section2substructure1/1'>second section</scene> by a β strand <scene name='Sandbox_Reserved_321/B-3/1'>(B-3)</scene> that crosses over the two domains, and leads into the second section initiating at the third α helix <scene name='Sandbox_Reserved_321/A-3/1'>(A-3)</scene><ref name ="making drugs for inhA">PMID:5882878</ref>. (A-3) is connected by a long loop to a 14 residue β strand <scene name='Sandbox_Reserved_321/B-4/2'>(B-4)</scene>that then leads into the fourth α helix <scene name='Sandbox_Reserved_321/A-4/2'>(A-4)</scene><ref name ="making drugs for inhA">PMID:5882878</ref>. A-4 then leads into a fifth strand β <scene name='Sandbox_Reserved_321/B-5/1'>(B-5)</scene>, followed by a 25 residue α helix <scene name='Sandbox_Reserved_321/A-5/2'>(A-5)</scene>, and into the final strand β <scene name='Sandbox_Reserved_321/B-6/1'>(B-6)</scene><ref name ="making drugs for inhA" | + | The first section is connected to the <scene name='Sandbox_Reserved_321/Section2substructure1/1'>second section</scene> by a β strand <scene name='Sandbox_Reserved_321/B-3/1'>(B-3)</scene> that crosses over the two domains, and leads into the second section initiating at the third α helix <scene name='Sandbox_Reserved_321/A-3/1'>(A-3)</scene><ref name ="making drugs for inhA">PMID:5882878</ref>. (A-3) is connected by a long loop to a 14 residue β strand <scene name='Sandbox_Reserved_321/B-4/2'>(B-4)</scene>that then leads into the fourth α helix <scene name='Sandbox_Reserved_321/A-4/2'>(A-4)</scene><ref name ="making drugs for inhA">PMID:5882878</ref>. A-4 then leads into a fifth strand β <scene name='Sandbox_Reserved_321/B-5/1'>(B-5)</scene>, followed by a 25 residue α helix <scene name='Sandbox_Reserved_321/A-5/2'>(A-5)</scene>, and into the final strand β <scene name='Sandbox_Reserved_321/B-6/1'>(B-6)</scene><ref name ="making drugs for inhA"/>. |
===Substructure 2 of inhA=== | ===Substructure 2 of inhA=== | ||
Revision as of 17:42, 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 |
Image:Secondary Structure of inhA.png
Secondary structure succession inhA.
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
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
