4z8d
From Proteopedia
(Difference between revisions)
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</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=4LB:TRANS-4-[({[(2-CHLOROBENZYL)OXY]CARBONYL}AMINO)METHYL]CYCLOHEXANECARBOXYLIC+ACID'>4LB</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=4LB:TRANS-4-[({[(2-CHLOROBENZYL)OXY]CARBONYL}AMINO)METHYL]CYCLOHEXANECARBOXYLIC+ACID'>4LB</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/Beta-ketoacyl-[acyl-carrier-protein]_synthase_III Beta-ketoacyl-[acyl-carrier-protein] synthase III], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.3.1.180 2.3.1.180] </span></td></tr> | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Beta-ketoacyl-[acyl-carrier-protein]_synthase_III Beta-ketoacyl-[acyl-carrier-protein] synthase III], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.3.1.180 2.3.1.180] </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=4z8d FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4z8d OCA], [http://pdbe.org/4z8d PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4z8d RCSB], [http://www.ebi.ac.uk/pdbsum/4z8d PDBsum]</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=4z8d FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4z8d OCA], [http://pdbe.org/4z8d PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4z8d RCSB], [http://www.ebi.ac.uk/pdbsum/4z8d PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4z8d ProSAT]</span></td></tr> |
</table> | </table> | ||
== Function == | == Function == | ||
[[http://www.uniprot.org/uniprot/FABH_ECO57 FABH_ECO57]] Catalyzes the condensation reaction of fatty acid synthesis by the addition to an acyl acceptor of two carbons from malonyl-ACP. Catalyzes the first condensation reaction which initiates fatty acid synthesis and may therefore play a role in governing the total rate of fatty acid production. Possesses both acetoacetyl-ACP synthase and acetyl transacylase activities. Its substrate specificity determines the biosynthesis of branched-chain and/or straight-chain of fatty acids.[HAMAP-Rule:MF_01815] | [[http://www.uniprot.org/uniprot/FABH_ECO57 FABH_ECO57]] Catalyzes the condensation reaction of fatty acid synthesis by the addition to an acyl acceptor of two carbons from malonyl-ACP. Catalyzes the first condensation reaction which initiates fatty acid synthesis and may therefore play a role in governing the total rate of fatty acid production. Possesses both acetoacetyl-ACP synthase and acetyl transacylase activities. Its substrate specificity determines the biosynthesis of branched-chain and/or straight-chain of fatty acids.[HAMAP-Rule:MF_01815] | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Fatty acid biosynthesis is essential to bacterial growth in Gram-negative pathogens. Several small molecules identified through a combination of high-throughput and fragment screening were cocrystallized with FabH (beta-ketoacyl-acyl carrier protein synthase III) from Escherichia coli and Streptococcus pneumoniae. Structure-based drug design was used to merge several scaffolds to provide a new class of inhibitors. After optimization for Gram-negative enzyme inhibitory potency, several compounds demonstrated antimicrobial activity against an efflux-negative strain of Haemophilus influenzae. Mutants resistant to these compounds had mutations in the FabH gene near the catalytic triad, validating FabH as a target for antimicrobial drug discovery. | ||
| + | |||
| + | Antibacterial FabH Inhibitors with Mode of Action Validated in Haemophilus influenzae by in Vitro Resistance Mutation Mapping.,McKinney DC, Eyermann CJ, Gu RF, Hu J, Kazmirski SL, Lahiri SD, McKenzie AR, Shapiro AB, Breault G ACS Infect Dis. 2016 Jul 8;2(7):456-64. doi: 10.1021/acsinfecdis.6b00053. Epub, 2016 May 9. PMID:27626097<ref>PMID:27626097</ref> | ||
| + | |||
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 4z8d" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
Revision as of 09:24, 3 October 2016
Antibacterial FabH Inhibitors with Validated Mode of Action in Haemophilus Influenzae by in vitro resistance mutation mapping
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