1ajp: Difference between revisions

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-[[Image:1ajp.gif|left|200px]]<br />
-<applet load="1ajp" size="450" color="white" frame="true" align="right" spinBox="true"
-caption="1ajp, resolution 2.31&Aring;" />
-'''PENICILLIN ACYLASE COMPLEXED WITH 2,5-DIHYDROXYPHENYLACETIC ACID'''<br />
-==Overview==
+==PENICILLIN ACYLASE COMPLEXED WITH 2,5-DIHYDROXYPHENYLACETIC ACID==
-The enzyme penicillin acylase (penicillin amidohydrolase EC 3.5.1. 11), catalyses the cleavage of the amide bond in the benzylpenicillin, (penicillin G) side-chain to produce phenylacetic acid and, 6-aminopenicillanic acid (6-APA). The enzyme is of great pharmaceutical, importance, as the product 6-APA is the starting point for the synthesis, of many semi-synthetic penicillin antibiotics. Studies have shown that the, enzyme is specific for hydrolysis of phenylacetamide derivatives, but is, more tolerant of features in the rest of the substrate. It is this, property that has led to many other applications for the enzyme, and, greater knowledge of the enzyme's structure and specificity could, facilitate engineering of the enzyme, enhancing its potential for chemical, and industrial applications.An extensive study of the binding of a series, of phenylacetic acid derivatives has been carried out. A measure of the, relative degree of inhibition of the enzyme by each of the compounds has, been obtained using a competitive inhibition assay, and the structures of, a number of these complexes have been determined by X-ray crystallography., The structures reveal a clear rationale for the observed kinetic results, but show also that some of the ligands cause a conformational change, within the binding pocket. This change can generally be understood in, terms of the size and orientation of the ligand within the active site.The, results reveal that ligand binding in penicillin acylase is facilitated by, certain amino acid residues that can adopt two distinct, energetically, favourable positions in order to accommodate a variety of compounds within, the active site. The structures of these complexes provide evidence for, conformational changes in the substrate-binding region that may act as a, switch in the mechanism of autocatalytic processing of this enzyme.
+<StructureSection load='1ajp' size='340' side='right'caption='[[1ajp]], [[Resolution|resolution]] 2.31&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[1ajp]] 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=1AJP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1AJP FirstGlance]. <br>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.31&#8491;</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=OMD:2-(3,6-DIHYDROXYPHENYL)ACETIC+ACID'>OMD</scene></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=1ajp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ajp OCA], [https://pdbe.org/1ajp PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1ajp RCSB], [https://www.ebi.ac.uk/pdbsum/1ajp PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1ajp ProSAT]</span></td></tr>
+</table>
+== Function ==
+[https://www.uniprot.org/uniprot/PAC_ECOLX PAC_ECOLX]
+== Evolutionary Conservation ==
+[[Image:Consurf_key_small.gif|200px|right]]
+Check<jmol>
+  <jmolCheckbox>
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/aj/1ajp_consurf.spt"</scriptWhenChecked>
+    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked>
+    <text>to colour the structure by Evolutionary Conservation</text>
+  </jmolCheckbox>
+</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=1ajp ConSurf].
+<div style="clear:both"></div>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+The enzyme penicillin acylase (penicillin amidohydrolase EC 3.5.1. 11) catalyses the cleavage of the amide bond in the benzylpenicillin (penicillin G) side-chain to produce phenylacetic acid and 6-aminopenicillanic acid (6-APA). The enzyme is of great pharmaceutical importance, as the product 6-APA is the starting point for the synthesis of many semi-synthetic penicillin antibiotics. Studies have shown that the enzyme is specific for hydrolysis of phenylacetamide derivatives, but is more tolerant of features in the rest of the substrate. It is this property that has led to many other applications for the enzyme, and greater knowledge of the enzyme's structure and specificity could facilitate engineering of the enzyme, enhancing its potential for chemical and industrial applications. An extensive study of the binding of a series of phenylacetic acid derivatives has been carried out. A measure of the relative degree of inhibition of the enzyme by each of the compounds has been obtained using a competitive inhibition assay, and the structures of a number of these complexes have been determined by X-ray crystallography. The structures reveal a clear rationale for the observed kinetic results, but show also that some of the ligands cause a conformational change within the binding pocket. This change can generally be understood in terms of the size and orientation of the ligand within the active site.The results reveal that ligand binding in penicillin acylase is facilitated by certain amino acid residues that can adopt two distinct, energetically favourable positions in order to accommodate a variety of compounds within the active site. The structures of these complexes provide evidence for conformational changes in the substrate-binding region that may act as a switch in the mechanism of autocatalytic processing of this enzyme.
-==About this Structure==
+Ligand-induced conformational change in penicillin acylase.,Done SH, Brannigan JA, Moody PC, Hubbard RE J Mol Biol. 1998 Nov 27;284(2):463-75. PMID:9813130<ref>PMID:9813130</ref>
-AJP is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli] with CA and OMD as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Penicillin_amidase Penicillin amidase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.5.1.11 3.5.1.11] Structure known Active Sites: CAA and CAT. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1AJP OCA].
-==Reference==
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-Ligand-induced conformational change in penicillin acylase., Done SH, Brannigan JA, Moody PC, Hubbard RE, J Mol Biol. 1998 Nov 27;284(2):463-75. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=9813130 9813130]
+</div>
+<div class="pdbe-citations 1ajp" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Penicillin acylase|Penicillin acylase]]
+== References ==
+<references/>
+__TOC__
+</StructureSection>
 [[Category: Escherichia coli]]
-[[Category: Penicillin amidase]]
+[[Category: Large Structures]]
-[[Category: Protein complex]]
+[[Category: Done SH]]
-[[Category: Done, S.H.]]
-[[Category: CA]]
-[[Category: OMD]]
-[[Category: antibiotic resistance]]
-[[Category: hydrolase]]
-[[Category: ligand induced conformational change]]
-''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov  5 15:48:40 2007''