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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'''
| | ===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.
| | The line below this paragraph, {{ABSTRACT_PUBMED_17227913}}, adds the Publication Abstract to the page |
| | (as it appears on PubMed at http://www.pubmed.gov), where 17227913 is the PubMed ID number. |
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| | {{ABSTRACT_PUBMED_17227913}} |
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| ==About this Structure== | | ==About this Structure== |
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| [[Category: Leprosy]] | | [[Category: Leprosy]] |
| [[Category: Prothionamide]] | | [[Category: Prothionamide]] |
| ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 09:54:19 2008'' | | |
| | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jul 29 09:56:25 2008'' |
