1lxc: Difference between revisions

From Proteopedia
Jump to navigationJump to search
← Older edit
OCA (talk | contribs)
Bots, Bureaucrats, journal, Administrators
3,332,843 edits
No edit summary
OCA (talk | contribs)
Bots, Bureaucrats, journal, Administrators
3,332,843 edits
No edit summary
 
(One intermediate revision by the same user not shown)
Line 3: Line 3:
<StructureSection load='1lxc' size='340' side='right'caption='[[1lxc]], [[Resolution|resolution]] 2.40&Aring;' scene=''>
<StructureSection load='1lxc' size='340' side='right'caption='[[1lxc]], [[Resolution|resolution]] 2.40&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[1lxc]] is a 2 chain structure with 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=1LXC OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1LXC FirstGlance]. <br>
<table><tr><td colspan='2'>[[1lxc]] 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=1LXC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1LXC FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=AYM:3-(6-AMINOPYRIDIN-3-YL)-N-METHYL-N-[(1-METHYL-1H-INDOL-2-YL)METHYL]ACRYLAMIDE'>AYM</scene>, <scene name='pdbligand=NAD:NICOTINAMIDE-ADENINE-DINUCLEOTIDE'>NAD</scene></td></tr>
</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>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1c14|1c14]], [[1i2z|1i2z]], [[1i30|1i30]], [[1qg6|1qg6]], [[1lx6|1lx6]]</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=AYM:3-(6-AMINOPYRIDIN-3-YL)-N-METHYL-N-[(1-METHYL-1H-INDOL-2-YL)METHYL]ACRYLAMIDE'>AYM</scene>, <scene name='pdbligand=NAD:NICOTINAMIDE-ADENINE-DINUCLEOTIDE'>NAD</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'>[https://proteopedia.org/fgij/fg.htm?mol=1lxc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1lxc OCA], [https://pdbe.org/1lxc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1lxc RCSB], [https://www.ebi.ac.uk/pdbsum/1lxc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1lxc ProSAT]</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=1lxc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1lxc OCA], [http://pdbe.org/1lxc PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1lxc RCSB], [http://www.ebi.ac.uk/pdbsum/1lxc PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1lxc ProSAT]</span></td></tr>
</table>
</table>
== Function ==
== Function ==
[[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>
[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 ==
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
[[Image:Consurf_key_small.gif|200px|right]]
Line 21: Line 20:
</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=1lxc ConSurf].
</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=1lxc ConSurf].
<div style="clear:both"></div>
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
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.
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<ref>PMID:12109908</ref>
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 1lxc" style="background-color:#fffaf0;"></div>


==See Also==
==See Also==
Line 39: Line 29:
[[Category: Escherichia coli]]
[[Category: Escherichia coli]]
[[Category: Large Structures]]
[[Category: Large Structures]]
[[Category: Berry, W E]]
[[Category: Berry WE]]
[[Category: Burgess, W J]]
[[Category: Burgess WJ]]
[[Category: Dewolf, V]]
[[Category: Dewolf V]]
[[Category: Head, M S]]
[[Category: Head MS]]
[[Category: Heerding, D A]]
[[Category: Heerding DA]]
[[Category: Huffman, W F]]
[[Category: Huffman WF]]
[[Category: Janson, C A]]
[[Category: Janson CA]]
[[Category: Keller, P M]]
[[Category: Keller PM]]
[[Category: Miller, W H]]
[[Category: Miller WH]]
[[Category: Moore, T D]]
[[Category: Moore TD]]
[[Category: Newlander, K A]]
[[Category: Newlander KA]]
[[Category: Payne, D J]]
[[Category: Payne DJ]]
[[Category: Pearson, S C]]
[[Category: Pearson SC]]
[[Category: Polizzi, B J]]
[[Category: Polizzi BJ]]
[[Category: Qiu, X]]
[[Category: Qiu X]]
[[Category: Rittenhouse, S F]]
[[Category: Rittenhouse SF]]
[[Category: Seefeld, M A]]
[[Category: Seefeld MA]]
[[Category: Uzinskas, I N]]
[[Category: Uzinskas IN]]
[[Category: Yuan, C C.K]]
[[Category: Yuan CCK]]
[[Category: Enoyl reductase]]
[[Category: Fabi]]
[[Category: Oxidoreductase]]
Retrieved from "https://proteopedia.org/1lxc"