1mfp

<StructureSection load='1mfp' size='340' side='right' caption='[[1mfp]], [[Resolution|resolution]] 2.33&Aring;' scene=''>

<table><tr><td colspan='2'>[[1mfp]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/"bacillus_coli"_migula_1895 "bacillus coli" migula 1895]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1MFP OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1MFP FirstGlance]. <br>

</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=IDN:(E)-N-METHYL-N-(1-METHYL-1H-INDOL-3-YLMETHYL)-3-(7-OXO-5,6,7,8-TETRAHYDRO-[1,8]NAPHTHYRIDIN-3-YL)-ACRYLAMIDE'>IDN</scene>, <scene name='pdbligand=NAD:NICOTINAMIDE-ADENINE-DINUCLEOTIDE'>NAD</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>

<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><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></td></tr>

<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1mfp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1mfp OCA], [http://pdbe.org/1mfp PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1mfp RCSB], [http://www.ebi.ac.uk/pdbsum/1mfp PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1mfp ProSAT]</span></td></tr>

[[http://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>

<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/mf/1mfp_consurf.spt"</scriptWhenChecked>

<div style="background-color:#fffaf0;">

== Publication Abstract from PubMed ==

Bacterial enoyl-ACP reductase (FabI) is responsible for catalyzing the final step of bacterial fatty acid biosynthesis and is an attractive target for the development of novel antibacterial agents. Previously we reported the development of FabI inhibitor 4 with narrow spectrum antimicrobial activity and in vivo efficacy against Staphylococcus aureus via intraperitoneal (ip) administration. Through iterative medicinal chemistry aided by X-ray crystal structure analysis, a new series of inhibitors has been developed with greatly increased potency against FabI-containing organisms. Several of these new inhibitors have potent antibacterial activity against multidrug resistant strains of S. aureus, and compound 30 demonstrates exceptional oral (po) in vivo efficacy in a S. aureus infection model in rats. While optimizing FabI inhibitory activity, compounds 29 and 30 were identified as having low micromolar FabK inhibitory activity, thereby increasing the antimicrobial spectrum of these compounds to include the FabK-containing pathogens Streptococcus pneumoniae and Enterococcus faecalis. The results described herein support the hypothesis that bacterial enoyl-ACP reductases are valid targets for antibacterial agents.

Indole naphthyridinones as inhibitors of bacterial enoyl-ACP reductases FabI and FabK.,Seefeld MA, Miller WH, Newlander KA, Burgess WJ, DeWolf WE Jr, Elkins PA, Head MS, Jakas DR, Janson CA, Keller PM, Manley PJ, Moore TD, Payne DJ, Pearson S, Polizzi BJ, Qiu X, Rittenhouse SF, Uzinskas IN, Wallis NG, Huffman WF J Med Chem. 2003 Apr 24;46(9):1627-35. PMID:12699381<ref>PMID:12699381</ref>

 

<div class="pdbe-citations 1mfp" style="background-color:#fffaf0;"></div>

[[Category: Bacillus coli migula 1895]]

[[Category: Burgess, W J]]

[[Category: DeWolf, W E]]

[[Category: Elkins, P A]]

[[Category: Head, M S]]

[[Category: Huffman, W F]]

[[Category: Jakas, D R]]

[[Category: Janson, C A]]

[[Category: Keller, P M]]

[[Category: Manley, P J]]

[[Category: Miller, W H]]

[[Category: Moore, T D]]

[[Category: Newlander, K A]]

[[Category: Payne, D J]]

[[Category: Pearson, S]]

[[Category: Polizzi, B J]]

[[Category: Qiu, X]]

[[Category: Rittenhouse, S F]]

[[Category: Seefeld, M A]]

[[Category: Uzinskas, I N]]

[[Category: Wallis, N G]]

[[Category: Oxidoreductase]]