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[[Image:1lx6.jpg|left|200px]]


{{Structure
==Crystal Structure of E. Coli Enoyl Reductase-NAD+ with a Bound Benzamide Inhibitor==
|PDB= 1lx6 |SIZE=350|CAPTION= <scene name='initialview01'>1lx6</scene>, resolution 2.40&Aring;
<StructureSection load='1lx6' size='340' side='right'caption='[[1lx6]], [[Resolution|resolution]] 2.40&Aring;' scene=''>
|SITE=  
== Structural highlights ==
|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>
<table><tr><td colspan='2'>[[1lx6]] is a 2 chain structure with sequence from [https://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]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1LX6 FirstGlance]. <br>
|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]
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.4&#8491;</td></tr>
|GENE=  
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><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></td></tr>
}}
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1lx6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1lx6 OCA], [https://pdbe.org/1lx6 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1lx6 RCSB], [https://www.ebi.ac.uk/pdbsum/1lx6 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1lx6 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/FABI_ECOLI FABI_ECOLI] Catalyzes the reduction of a carbon-carbon double bond in an enoyl moiety that is covalently linked to an acyl carrier protein (ACP). Involved in the elongation cycle of fatty acid which are used in the lipid metabolism and in the biotin biosynthesis.<ref>PMID:8119879</ref> <ref>PMID:7592873</ref> <ref>PMID:20693992</ref>
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/lx/1lx6_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1lx6 ConSurf].
<div style="clear:both"></div>


'''Crystal Structure of E. Coli Enoyl Reductase-NAD+ with a Bound Benzamide Inhibitor'''
==See Also==
 
*[[Enoyl-Acyl-Carrier Protein Reductase 3D structures|Enoyl-Acyl-Carrier Protein Reductase 3D structures]]
 
== References ==
==Overview==
<references/>
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.
__TOC__
 
</StructureSection>
==About this Structure==
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==
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: Escherichia coli]]
[[Category: Escherichia coli]]
[[Category: Single protein]]
[[Category: Large Structures]]
[[Category: Janson, C A.]]
[[Category: Janson CA]]
[[Category: Qiu, X.]]
[[Category: Qiu X]]
[[Category: Smith, W W.]]
[[Category: Smith WW]]
[[Category: NAD]]
[[Category: ZAM]]
[[Category: enoyl reductase]]
[[Category: fabi]]
[[Category: oxidoreductase]]
 
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 12:36:15 2008''

Latest revision as of 07:37, 14 February 2024

Crystal Structure of E. Coli Enoyl Reductase-NAD+ with a Bound Benzamide Inhibitor

1lx6, resolution 2.40Å

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