1kec

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[[Image:1kec.jpg|left|200px]]
 
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==PENICILLIN ACYLASE MUTANT WITH PHENYL PROPRIONIC ACID==
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The line below this paragraph, containing "STRUCTURE_1kec", creates the "Structure Box" on the page.
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<StructureSection load='1kec' size='340' side='right'caption='[[1kec]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
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You may change the PDB parameter (which sets the PDB file loaded into the applet)
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== Structural highlights ==
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or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
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<table><tr><td colspan='2'>[[1kec]] 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=1KEC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1KEC FirstGlance]. <br>
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or leave the SCENE parameter empty for the default display.
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.3&#8491;</td></tr>
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<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>
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{{STRUCTURE_1kec| PDB=1kec | SCENE= }}
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<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>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/PAC_ECOLX PAC_ECOLX]
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ke/1kec_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</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=1kec ConSurf].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Penicillin 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.
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'''PENICILLIN ACYLASE MUTANT WITH PHENYL PROPRIONIC ACID'''
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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<ref>PMID:15254299</ref>
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==Overview==
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Penicillin 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.
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==About this Structure==
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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1KEC is a [[Protein complex]] structure of sequences 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=1KEC OCA].
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</div>
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<div class="pdbe-citations 1kec" style="background-color:#fffaf0;"></div>
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==Reference==
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==See Also==
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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:[http://www.ncbi.nlm.nih.gov/pubmed/15254299 15254299]
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*[[Penicillin acylase|Penicillin acylase]]
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== References ==
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<references/>
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__TOC__
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</StructureSection>
[[Category: Escherichia coli]]
[[Category: Escherichia coli]]
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[[Category: Penicillin amidase]]
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[[Category: Large Structures]]
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[[Category: Protein complex]]
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[[Category: Dijkstra BW]]
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[[Category: Dijkstra, B W.]]
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[[Category: Hensgens CMH]]
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[[Category: Hensgens, C M.H.]]
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[[Category: Keizer E]]
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[[Category: Keizer, E.]]
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[[Category: Snijder HJ]]
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[[Category: Snijder, H J.]]
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[[Category: Beta-strand]]
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[[Category: Helice]]
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[[Category: Ntn-hydrolase fold]]
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[[Category: Phenyl proprionic acid]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May 2 22:38:19 2008''
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Current revision

PENICILLIN ACYLASE MUTANT WITH PHENYL PROPRIONIC ACID

PDB ID 1kec

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