1lx6
From Proteopedia
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|PDB= 1lx6 |SIZE=350|CAPTION= <scene name='initialview01'>1lx6</scene>, resolution 2.40Å | |PDB= 1lx6 |SIZE=350|CAPTION= <scene name='initialview01'>1lx6</scene>, resolution 2.40Å | ||
|SITE= | |SITE= | ||
| - | |LIGAND= <scene name='pdbligand=NAD:NICOTINAMIDE-ADENINE-DINUCLEOTIDE'>NAD</scene> | + | |LIGAND= <scene name='pdbligand=NAD:NICOTINAMIDE-ADENINE-DINUCLEOTIDE'>NAD</scene>, <scene name='pdbligand=ZAM:3-[(ACETYL-METHYL-AMINO)-METHYL]-4-AMINO-N-METHYL-N-(1-METHYL-1H-INDOL-2-YLMETHYL)-BENZAMIDE'>ZAM</scene> |
| - | |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] | + | |ACTIVITY= <span class='plainlinks'>[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] </span> |
|GENE= | |GENE= | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY=[[1c14|1C14]], [[1i2z|1I2Z]], [[1i30|1I30]], [[1qg6|1QG6]], [[1lxc|1lxc]] | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1lx6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1lx6 OCA], [http://www.ebi.ac.uk/pdbsum/1lx6 PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1lx6 RCSB]</span> | ||
}} | }} | ||
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[[Category: Qiu, X.]] | [[Category: Qiu, X.]] | ||
[[Category: Smith, W W.]] | [[Category: Smith, W W.]] | ||
| - | [[Category: NAD]] | ||
| - | [[Category: ZAM]] | ||
[[Category: enoyl reductase]] | [[Category: enoyl reductase]] | ||
[[Category: fabi]] | [[Category: fabi]] | ||
[[Category: oxidoreductase]] | [[Category: oxidoreductase]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 22:08:29 2008'' |
Revision as of 19:08, 30 March 2008
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| , resolution 2.40Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | , | ||||||
| Activity: | [acyl-carrier-protein_reductase_(NADH) Enoyl-[acyl-carrier-protein] reductase (NADH)], with EC number 1.3.1.9 | ||||||
| Related: | 1C14, 1I2Z, 1I30, 1QG6, 1lxc
| ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Crystal Structure of E. Coli Enoyl Reductase-NAD+ with a Bound Benzamide Inhibitor
Overview
Bacterial enoyl-ACP reductase (FabI) catalyzes the final step in each cycle of bacterial fatty acid biosynthesis and is an attractive target for the development of new antibacterial agents. Our efforts to identify potent, selective FabI inhibitors began with screening of the GlaxoSmithKline proprietary compound collection, which identified several small-molecule inhibitors of Staphylococcus aureus FabI. Through a combination of iterative medicinal chemistry and X-ray crystal structure based design, one of these leads was developed into the novel aminopyridine derivative 9, a low micromolar inhibitor of FabI from S. aureus (IC(50) = 2.4 microM) and Haemophilus influenzae (IC(50) = 4.2 microM). Compound 9 has good in vitro antibacterial activity against several organisms, including S. aureus (MIC = 0.5 microg/mL), and is effective in vivo in a S. aureus groin abscess infection model in rats. Through FabI overexpressor and macromolecular synthesis studies, the mode of action of 9 has been confirmed to be inhibition of fatty acid biosynthesis via inhibition of FabI. Taken together, these results support FabI as a valid antibacterial target and demonstrate the potential of small-molecule FabI inhibitors for the treatment of bacterial infections.
About this Structure
1LX6 is a Single protein structure of sequence from Escherichia coli. Full crystallographic information is available from OCA.
Reference
Discovery of aminopyridine-based inhibitors of bacterial enoyl-ACP reductase (FabI)., Miller WH, Seefeld MA, Newlander KA, Uzinskas IN, Burgess WJ, Heerding DA, Yuan CC, Head MS, Payne DJ, Rittenhouse SF, Moore TD, Pearson SC, Berry V, DeWolf WE Jr, Keller PM, Polizzi BJ, Qiu X, Janson CA, Huffman WF, J Med Chem. 2002 Jul 18;45(15):3246-56. PMID:12109908 [[Category: Enoyl-[acyl-carrier-protein] reductase (NADH)]]
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