1kec: Difference between revisions
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<StructureSection load='1kec' size='340' side='right'caption='[[1kec]], [[Resolution|resolution]] 2.30Å' scene=''> | <StructureSection load='1kec' size='340' side='right'caption='[[1kec]], [[Resolution|resolution]] 2.30Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[1kec]] is a 2 chain structure with sequence from [ | <table><tr><td colspan='2'>[[1kec]] is a 2 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=1KEC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1KEC FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=GRO:R-2-PHENYL-PROPRIONIC+ACID'>GRO</scene></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=GRO:R-2-PHENYL-PROPRIONIC+ACID'>GRO</scene></td></tr> | ||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1pnk|1pnk]], [[1jx9|1jx9]], [[1k5q|1k5q]], [[1k5s|1k5s]], [[1k7d|1k7d]]</div></td></tr> | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1pnk|1pnk]], [[1jx9|1jx9]], [[1k5q|1k5q]], [[1k5s|1k5s]], [[1k7d|1k7d]]</div></td></tr> | ||
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PAC ([ | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PAC ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=562 "Bacillus coli" Migula 1895])</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/Penicillin_amidase Penicillin amidase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.5.1.11 3.5.1.11] </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=1kec FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1kec OCA], [https://pdbe.org/1kec PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1kec RCSB], [https://www.ebi.ac.uk/pdbsum/1kec PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1kec ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Evolutionary Conservation == | == Evolutionary Conservation == | ||
Revision as of 17:40, 27 October 2021
PENICILLIN ACYLASE MUTANT WITH PHENYL PROPRIONIC ACIDPENICILLIN ACYLASE MUTANT WITH PHENYL PROPRIONIC ACID
Structural highlights
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 PubMedPenicillin acylase catalyses the condensation of Calpha-substituted phenylacetic acids with beta-lactam nucleophiles, producing semi-synthetic beta-lactam antibiotics. For efficient synthesis a low affinity for phenylacetic acid and a high affinity for Calpha-substituted phenylacetic acid derivatives is desirable. We made three active site mutants, alphaF146Y, betaF24A and alphaF146Y/betaF24A, which all had a 2- to 10-fold higher affinity for Calpha-substituted compounds than wild-type enzyme. In addition, betaF24A had a 20-fold reduced affinity for phenylacetic acid. The molecular basis of the improved properties was investigated by X-ray crystallography. These studies showed that the higher affinity of alphaF146Y for (R)-alpha-methylphenylacetic acid can be explained by van der Waals interactions between alphaY146:OH and the Calpha-substituent. The betaF24A mutation causes an opening of the phenylacetic acid binding site. Only (R)-alpha-methylphenylacetic acid, but not phenylacetic acid, induces a conformation with the ligand tightly bound, explaining the weak binding of phenylacetic acid. A comparison of the betaF24A structure with other open conformations of penicillin acylase showed that betaF24 has a fixed position, whereas alphaF146 acts as a flexible lid on the binding site and reorients its position to achieve optimal substrate binding. Structural and kinetic studies on ligand binding in wild-type and active-site mutants of penicillin acylase.,Alkema WB, Hensgens CM, Snijder HJ, Keizer E, Dijkstra BW, Janssen DB Protein Eng Des Sel. 2004 May;17(5):473-80. Epub 2004 Jul 14. PMID:15254299[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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