2nv6
From Proteopedia
(New page: 200px<br /><applet load="2nv6" size="450" color="white" frame="true" align="right" spinBox="true" caption="2nv6, resolution 1.90Å" /> '''Mycobacterium tuberc...) |
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| - | [[Image:2nv6.gif|left|200px]]<br /><applet load="2nv6" size=" | + | [[Image:2nv6.gif|left|200px]]<br /><applet load="2nv6" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="2nv6, resolution 1.90Å" /> | caption="2nv6, resolution 1.90Å" /> | ||
'''Mycobacterium tuberculosis InhA (S94A) bound with INH-NAD adduct'''<br /> | '''Mycobacterium tuberculosis InhA (S94A) bound with INH-NAD adduct'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Isoniazid is one of the most effective antituberculosis drugs, yet its | + | Isoniazid is one of the most effective antituberculosis drugs, yet its precise mechanism of action is still controversial. Using specialized linkage transduction, a single point mutation allele (S94A) within the putative target gene inhA was transferred in Mycobacterium tuberculosis. The inhA(S94A) allele was sufficient to confer clinically relevant levels of resistance to isoniazid killing and inhibition of mycolic acid biosynthesis. This resistance correlated with the decreased binding of the INH-NAD inhibitor to InhA, as shown by enzymatic and X-ray crystallographic analyses, and establishes InhA as the primary target of isoniazid action in M. tuberculosis. |
==About this Structure== | ==About this Structure== | ||
| - | 2NV6 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Mycobacterium_tuberculosis Mycobacterium tuberculosis] with ZID as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/Enoyl-[acyl-carrier-protein]_reductase_(NADH) Enoyl-[acyl-carrier-protein] reductase (NADH)], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.3.1.9 1.3.1.9] Full crystallographic information is available from [http:// | + | 2NV6 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Mycobacterium_tuberculosis Mycobacterium tuberculosis] with <scene name='pdbligand=ZID:'>ZID</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/Enoyl-[acyl-carrier-protein]_reductase_(NADH) Enoyl-[acyl-carrier-protein] reductase (NADH)], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.3.1.9 1.3.1.9] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2NV6 OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Mycobacterium tuberculosis]] | [[Category: Mycobacterium tuberculosis]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Sacchettini, J | + | [[Category: Sacchettini, J C.]] |
[[Category: Wang, F.]] | [[Category: Wang, F.]] | ||
[[Category: ZID]] | [[Category: ZID]] | ||
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[[Category: tuberculosis]] | [[Category: tuberculosis]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 18:11:22 2008'' |
Revision as of 16:11, 21 February 2008
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Mycobacterium tuberculosis InhA (S94A) bound with INH-NAD adduct
Overview
Isoniazid is one of the most effective antituberculosis drugs, yet its precise mechanism of action is still controversial. Using specialized linkage transduction, a single point mutation allele (S94A) within the putative target gene inhA was transferred in Mycobacterium tuberculosis. The inhA(S94A) allele was sufficient to confer clinically relevant levels of resistance to isoniazid killing and inhibition of mycolic acid biosynthesis. This resistance correlated with the decreased binding of the INH-NAD inhibitor to InhA, as shown by enzymatic and X-ray crystallographic analyses, and establishes InhA as the primary target of isoniazid action in M. tuberculosis.
About this Structure
2NV6 is a Single protein structure of sequence from Mycobacterium tuberculosis with as ligand. Active as [acyl-carrier-protein_reductase_(NADH) Enoyl-[acyl-carrier-protein] reductase (NADH)], with EC number 1.3.1.9 Full crystallographic information is available from OCA.
Reference
Transfer of a point mutation in Mycobacterium tuberculosis inhA resolves the target of isoniazid., Vilcheze C, Wang F, Arai M, Hazbon MH, Colangeli R, Kremer L, Weisbrod TR, Alland D, Sacchettini JC, Jacobs WR Jr, Nat Med. 2006 Sep;12(9):1027-9. Epub 2006 Aug 13. PMID:16906155 [[Category: Enoyl-[acyl-carrier-protein] reductase (NADH)]]
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