2ntj: Difference between revisions
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New page: left|200px<br /><applet load="2ntj" size="450" color="white" frame="true" align="right" spinBox="true" caption="2ntj, resolution 2.50Å" /> '''Mycobacterium tuberc... |
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[[Image:2ntj.gif|left|200px]]<br /><applet load="2ntj" size=" | [[Image:2ntj.gif|left|200px]]<br /><applet load="2ntj" size="350" color="white" frame="true" align="right" spinBox="true" | ||
caption="2ntj, resolution 2.50Å" /> | caption="2ntj, resolution 2.50Å" /> | ||
'''Mycobacterium tuberculosis InhA bound with PTH-NAD adduct'''<br /> | '''Mycobacterium tuberculosis InhA bound with PTH-NAD adduct'''<br /> | ||
==Overview== | ==Overview== | ||
Thioamide drugs, ethionamide (ETH) and prothionamide (PTH), are clinically | 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== | ==About this Structure== | ||
2NTJ 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 P1H 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:// | 2NTJ 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=P1H:'>P1H</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=2NTJ 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: P1H]] | [[Category: P1H]] | ||
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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 18:10:50 2008'' | ||
