1lx6

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[[Image:1lx6.jpg|left|200px]]<br /><applet load="1lx6" size="350" color="white" frame="true" align="right" spinBox="true"
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[[Image:1lx6.jpg|left|200px]]
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caption="1lx6, resolution 2.40&Aring;" />
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'''Crystal Structure of E. Coli Enoyl Reductase-NAD+ with a Bound Benzamide Inhibitor'''<br />
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{{Structure
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|PDB= 1lx6 |SIZE=350|CAPTION= <scene name='initialview01'>1lx6</scene>, resolution 2.40&Aring;
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|SITE=
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|LIGAND= <scene name='pdbligand=NAD:NICOTINAMIDE-ADENINE-DINUCLEOTIDE'>NAD</scene> and <scene name='pdbligand=ZAM:3-[(ACETYL-METHYL-AMINO)-METHYL]-4-AMINO-N-METHYL-N-(1-METHYL-1H-INDOL-2-YLMETHYL)-BENZAMIDE'>ZAM</scene>
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|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]
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|GENE=
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}}
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'''Crystal Structure of E. Coli Enoyl Reductase-NAD+ with a Bound Benzamide Inhibitor'''
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==Overview==
==Overview==
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==About this Structure==
==About this Structure==
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1LX6 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli] with <scene name='pdbligand=NAD:'>NAD</scene> and <scene name='pdbligand=ZAM:'>ZAM</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. 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=1LX6 OCA].
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1LX6 is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1LX6 OCA].
==Reference==
==Reference==
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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:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=12109908 12109908]
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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:[http://www.ncbi.nlm.nih.gov/pubmed/12109908 12109908]
[[Category: Enoyl-[acyl-carrier-protein] reductase (NADH)]]
[[Category: Enoyl-[acyl-carrier-protein] reductase (NADH)]]
[[Category: Escherichia coli]]
[[Category: Escherichia coli]]
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[[Category: oxidoreductase]]
[[Category: oxidoreductase]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:49:19 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 12:36:15 2008''

Revision as of 10:36, 20 March 2008

Image:1lx6.jpg


PDB ID 1lx6

Drag the structure with the mouse to rotate
, resolution 2.40Å
Ligands: and
Activity: [acyl-carrier-protein_reductase_(NADH) Enoyl-[acyl-carrier-protein] reductase (NADH)], with EC number 1.3.1.9
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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