2h9i

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[[Image:2h9i.jpg|left|200px]]<br /><applet load="2h9i" size="350" color="white" frame="true" align="right" spinBox="true"
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[[Image:2h9i.jpg|left|200px]]
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caption="2h9i, resolution 2.200&Aring;" />
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'''Mycobacterium tuberculosis InhA bound with ETH-NAD adduct'''<br />
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{{Structure
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|PDB= 2h9i |SIZE=350|CAPTION= <scene name='initialview01'>2h9i</scene>, resolution 2.200&Aring;
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|SITE=
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|LIGAND= <scene name='pdbligand=EAD:{(2R,3S,4R,5R)-5-[(4S)-3-(AMINOCARBONYL)-4-(2-ETHYLISONICOTINOYL)PYRIDIN-1(4H)-YL]-3,4-DIHYDROXYTETRAHYDROFURAN-2-YL}METHYL [(2R,3S,4R,5R)-5-(6-AMINO-9H-PURIN-9-YL)-3,4-DIHYDROXYTETRAHYDROFURAN-2-YL]METHYL DIHYDROGEN DIPHOSPHATE'>EAD</scene>
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|ACTIVITY= [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]
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|GENE= inhA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1773 Mycobacterium tuberculosis])
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}}
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'''Mycobacterium tuberculosis InhA bound with ETH-NAD adduct'''
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==Overview==
==Overview==
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==About this Structure==
==About this Structure==
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2H9I 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=EAD:'>EAD</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=2H9I OCA].
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2H9I is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Mycobacterium_tuberculosis Mycobacterium tuberculosis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2H9I OCA].
==Reference==
==Reference==
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Mechanism of thioamide drug action against tuberculosis and leprosy., Wang F, Langley R, Gulten G, Dover LG, Besra GS, Jacobs WR Jr, Sacchettini JC, J Exp Med. 2007 Jan 22;204(1):73-8. Epub 2007 Jan 16. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=17227913 17227913]
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Mechanism of thioamide drug action against tuberculosis and leprosy., Wang F, Langley R, Gulten G, Dover LG, Besra GS, Jacobs WR Jr, Sacchettini JC, J Exp Med. 2007 Jan 22;204(1):73-8. Epub 2007 Jan 16. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/17227913 17227913]
[[Category: Enoyl-[acyl-carrier-protein] reductase (NADH)]]
[[Category: Enoyl-[acyl-carrier-protein] reductase (NADH)]]
[[Category: Mycobacterium tuberculosis]]
[[Category: Mycobacterium tuberculosis]]
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[[Category: tuberculosis]]
[[Category: tuberculosis]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 17:39:34 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 17:14:18 2008''

Revision as of 15:14, 20 March 2008

Image:2h9i.jpg


PDB ID 2h9i

Drag the structure with the mouse to rotate
, resolution 2.200Å
Ligands:
Gene: inhA (Mycobacterium tuberculosis)
Activity: [acyl-carrier-protein_reductase_(NADH) Enoyl-[acyl-carrier-protein] reductase (NADH)], with EC number 1.3.1.9
Coordinates: save as pdb, mmCIF, xml



Mycobacterium tuberculosis InhA bound with ETH-NAD adduct


Overview

Thioamide drugs, ethionamide (ETH) and prothionamide (PTH), are clinically effective in the treatment of Mycobacterium tuberculosis, M. leprae, and M. avium complex infections. Although generally considered second-line drugs for tuberculosis, their use has increased considerably as the number of multidrug resistant and extensively drug resistant tuberculosis cases continues to rise. Despite the widespread use of thioamide drugs to treat tuberculosis and leprosy, their precise mechanisms of action remain unknown. Using a cell-based activation method, we now have definitive evidence that both thioamides form covalent adducts with nicotinamide adenine dinucleotide (NAD) and that these adducts are tight-binding inhibitors of M. tuberculosis and M. leprae InhA. The crystal structures of the inhibited M. leprae and M. tuberculosis InhA complexes provide the molecular details of target-drug interactions. The purified ETH-NAD and PTH-NAD adducts both showed nanomolar Kis against M. tuberculosis and M. leprae InhA. Knowledge of the precise structures and mechanisms of action of these drugs provides insights into designing new drugs that can overcome drug resistance.

About this Structure

2H9I is a Single protein structure of sequence from Mycobacterium tuberculosis. Full crystallographic information is available from OCA.

Reference

Mechanism of thioamide drug action against tuberculosis and leprosy., Wang F, Langley R, Gulten G, Dover LG, Besra GS, Jacobs WR Jr, Sacchettini JC, J Exp Med. 2007 Jan 22;204(1):73-8. Epub 2007 Jan 16. PMID:17227913 [[Category: Enoyl-[acyl-carrier-protein] reductase (NADH)]]

Page seeded by OCA on Thu Mar 20 17:14:18 2008

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