1fj4: Difference between revisions
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<StructureSection load='1fj4' size='340' side='right'caption='[[1fj4]], [[Resolution|resolution]] 2.35Å' scene=''> | <StructureSection load='1fj4' size='340' side='right'caption='[[1fj4]], [[Resolution|resolution]] 2.35Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[1fj4]] is a 4 chain structure with sequence from [ | <table><tr><td colspan='2'>[[1fj4]] is a 4 chain structure with sequence from [https://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=1FJ4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1FJ4 FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=TLM:THIOLACTOMYCIN'>TLM</scene></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=TLM:THIOLACTOMYCIN'>TLM</scene></td></tr> | ||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1fj8|1fj8]], [[1b3n|1b3n]]</td></tr> | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1fj8|1fj8]], [[1b3n|1b3n]]</div></td></tr> | ||
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[ | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Beta-ketoacyl-[acyl-carrier-protein]_synthase_I Beta-ketoacyl-[acyl-carrier-protein] synthase I], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.3.1.41 2.3.1.41] </span></td></tr> | ||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1fj4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1fj4 OCA], [https://pdbe.org/1fj4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1fj4 RCSB], [https://www.ebi.ac.uk/pdbsum/1fj4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1fj4 ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | == Function == | ||
[[ | [[https://www.uniprot.org/uniprot/FABB_ECOLI FABB_ECOLI]] Catalyzes the condensation reaction of fatty acid synthesis by the addition to an acyl acceptor of two carbons from malonyl-ACP. Specific for elongation from C-10 to unsaturated C-16 and C-18 fatty acids. | ||
== Evolutionary Conservation == | == Evolutionary Conservation == | ||
[[Image:Consurf_key_small.gif|200px|right]] | [[Image:Consurf_key_small.gif|200px|right]] | ||
Revision as of 14:10, 28 July 2021
THE STRUCTURE OF BETA-KETOACYL-[ACYL CARRIER PROTEIN] SYNTHASE I IN COMPLEX WITH THIOLACTOMYCIN, IMPLICATIONS FOR DRUG DESIGNTHE STRUCTURE OF BETA-KETOACYL-[ACYL CARRIER PROTEIN] SYNTHASE I IN COMPLEX WITH THIOLACTOMYCIN, IMPLICATIONS FOR DRUG DESIGN
Structural highlights
Function[FABB_ECOLI] Catalyzes the condensation reaction of fatty acid synthesis by the addition to an acyl acceptor of two carbons from malonyl-ACP. Specific for elongation from C-10 to unsaturated C-16 and C-18 fatty acids. Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedThe beta-ketoacyl-acyl carrier protein (ACP) synthases are key regulators of type II fatty acid synthesis and are the targets for two natural products, thiolactomycin (TLM) and cerulenin. The high resolution structures of the FabB-TLM and FabB-cerulenin binary complexes were determined. TLM mimics malonyl-ACP in the FabB active site. It forms strong hydrogen bond interactions with the two catalytic histidines, and the unsaturated alkyl side chain interaction with a small hydrophobic pocket is stabilized by pi stacking interactions. Cerulenin binding mimics the condensation transition state. The subtle differences between the FabB-cerulenin and FabF-cerulenin (Moche, M., Schneider, G., Edwards, P., Dehesh, K., and Lindqvist, Y. (1999) J. Biol. Chem. 244, 6031-6034) structures explain the differences in the sensitivity of the two enzymes to the antibiotic and may reflect the distinct substrate specificities that differentiate the two enzymes. The FabB[H333N] protein was prepared to convert the FabB His-His-Cys active site triad into the FabH His-Asn-Cys configuration to test the importance of the two His residues in TLM and cerulenin binding. FabB[H333N] was significantly more resistant to both antibiotics than FabB and had an affinity for TLM an order of magnitude less than the wild-type enzyme, illustrating that the two-histidine active site architecture is critical to protein-antibiotic interaction. These data provide a structural framework for understanding antibiotic sensitivity within this group of enzymes. Inhibition of beta-ketoacyl-acyl carrier protein synthases by thiolactomycin and cerulenin. Structure and mechanism.,Price AC, Choi KH, Heath RJ, Li Z, White SW, Rock CO J Biol Chem. 2001 Mar 2;276(9):6551-9. Epub 2000 Oct 24. PMID:11050088[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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