2ntv

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[[Image:2ntv.gif|left|200px]]
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{{Seed}}
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{{STRUCTURE_2ntv| PDB=2ntv | SCENE= }}
{{STRUCTURE_2ntv| PDB=2ntv | SCENE= }}
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'''Mycobacterium leprae InhA bound with PTH-NAD adduct'''
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===Mycobacterium leprae InhA bound with PTH-NAD adduct===
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==Overview==
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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.
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(as it appears on PubMed at http://www.pubmed.gov), where 17227913 is the PubMed ID number.
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{{ABSTRACT_PUBMED_17227913}}
==About this Structure==
==About this Structure==
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[[Category: Leprosy]]
[[Category: Leprosy]]
[[Category: Prothionamide]]
[[Category: Prothionamide]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 09:54:19 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jul 29 09:56:25 2008''

Revision as of 06:56, 29 July 2008

Image:2ntv.png

Template:STRUCTURE 2ntv

Mycobacterium leprae InhA bound with PTH-NAD adduct

Template:ABSTRACT PUBMED 17227913

About this Structure

2NTV is a Single protein structure of sequence from Mycobacterium leprae. 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

Page seeded by OCA on Tue Jul 29 09:56:25 2008

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