1p45

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|GENE= INHA OR RV1484 OR MT1531 OR MTCY277.05 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1773 Mycobacterium tuberculosis])
|GENE= INHA OR RV1484 OR MT1531 OR MTCY277.05 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1773 Mycobacterium tuberculosis])
|DOMAIN=<span class='plainlinks'>[http://www.ncbi.nlm.nih.gov/Structure/cdd/cddsrv.cgi?uid=COG0623 FabI], [http://www.ncbi.nlm.nih.gov/Structure/cdd/cddsrv.cgi?uid=PRK07889 PRK07889]</span>
|DOMAIN=<span class='plainlinks'>[http://www.ncbi.nlm.nih.gov/Structure/cdd/cddsrv.cgi?uid=COG0623 FabI], [http://www.ncbi.nlm.nih.gov/Structure/cdd/cddsrv.cgi?uid=PRK07889 PRK07889]</span>
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|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1p45 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1p45 OCA], [http://www.ebi.ac.uk/pdbsum/1p45 PDBsum], [http://www.fli-leibniz.de/cgi-bin/ImgLib.pl?CODE=1kfv JenaLib], [http://www.rcsb.org/pdb/explore.do?structureId=1p45 RCSB]</span>
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|RELATEDENTRY=[[1p44|1P44]]
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|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1p45 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1p45 OCA], [http://www.ebi.ac.uk/pdbsum/1p45 PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1p45 RCSB]</span>
}}
}}
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[[Category: triclosan]]
[[Category: triclosan]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Mar 26 06:00:19 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 22:54:40 2008''

Revision as of 19:54, 30 March 2008

Image:1p45.gif


PDB ID 1p45

Drag the structure with the mouse to rotate
, resolution 2.60Å
Ligands: ,
Gene: INHA OR RV1484 OR MT1531 OR MTCY277.05 (Mycobacterium tuberculosis)
Activity: [acyl-carrier-protein_reductase_(NADH) Enoyl-[acyl-carrier-protein] reductase (NADH)], with EC number 1.3.1.9
Domains: FabI, PRK07889
Related: 1P44


Resources: FirstGlance, OCA, PDBsum, RCSB
Coordinates: save as pdb, mmCIF, xml



Targeting tuberculosis and malaria through inhibition of enoyl reductase: compound activity and structural data


Overview

Tuberculosis and malaria together result in an estimated 5 million deaths annually. The spread of multidrug resistance in the most pathogenic causative agents, Mycobacterium tuberculosis and Plasmodium falciparum, underscores the need to identify active compounds with novel inhibitory properties. Although genetically unrelated, both organisms use a type II fatty-acid synthase system. Enoyl acyl carrier protein reductase (ENR), a key type II enzyme, has been repeatedly validated as an effective antimicrobial target. Using high throughput inhibitor screens with a combinatorial library, we have identified two novel classes of compounds with activity against the M. tuberculosis and P. falciparum enzyme (referred to as InhA and PfENR, respectively). The crystal structure of InhA complexed with NAD+ and one of the inhibitors was determined to elucidate the mode of binding. Structural analysis of InhA with the broad spectrum antimicrobial triclosan revealed a unique stoichiometry where the enzyme contained either a single triclosan molecule, in a configuration typical of other bacterial ENR:triclosan structures, or harbored two triclosan molecules bound to the active site. Significantly, these compounds do not require activation and are effective against wild-type and drug-resistant strains of M. tuberculosis and P. falciparum. Moreover, they provide broader chemical diversity and elucidate key elements of inhibitor binding to InhA for subsequent chemical optimization.

About this Structure

1P45 is a Single protein structure of sequence from Mycobacterium tuberculosis. Full crystallographic information is available from OCA.

Reference

Targeting tuberculosis and malaria through inhibition of Enoyl reductase: compound activity and structural data., Kuo MR, Morbidoni HR, Alland D, Sneddon SF, Gourlie BB, Staveski MM, Leonard M, Gregory JS, Janjigian AD, Yee C, Musser JM, Kreiswirth B, Iwamoto H, Perozzo R, Jacobs WR Jr, Sacchettini JC, Fidock DA, J Biol Chem. 2003 Jun 6;278(23):20851-9. Epub 2003 Feb 26. PMID:12606558 [[Category: Enoyl-[acyl-carrier-protein] reductase (NADH)]]

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