1mxo: Difference between revisions

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-[[Image:1mxo.png|left|200px]]
-{{STRUCTURE_1mxo|  PDB=1mxo  |  SCENE=  }}
+==AmpC beta-lactamase in complex with an m.carboxyphenylglycylboronic acid bearing the cephalothin R1 side chain==
+<StructureSection load='1mxo' size='340' side='right'caption='[[1mxo]], [[Resolution|resolution]] 1.83&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[1mxo]] 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=1MXO OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1MXO 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]] 1.83&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene>, <scene name='pdbligand=SM2:(1R)-1-(2-THIENYLACETYLAMINO)-1-(3-CARBOXYPHENYL)METHYLBORONIC+ACID'>SM2</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=1mxo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1mxo OCA], [https://pdbe.org/1mxo PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1mxo RCSB], [https://www.ebi.ac.uk/pdbsum/1mxo PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1mxo ProSAT]</span></td></tr>
+</table>
+== Function ==
+[https://www.uniprot.org/uniprot/AMPC_ECOLI AMPC_ECOLI] This protein is a serine beta-lactamase with a substrate specificity for cephalosporins.
+== 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/mx/1mxo_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=1mxo ConSurf].
+<div style="clear:both"></div>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+beta-lactamases are the most widespread resistance mechanism to beta-lactam antibiotics, such as the penicillins and the cephalosporins. In an effort to combat these enzymes, a combination of stereoselective organic synthesis, enzymology, microbiology, and X-ray crystallography was used to design and evaluate new carboxyphenyl-glycylboronic acid transition-state analogue inhibitors of the class C beta-lactamase AmpC. The new compounds improve inhibition by over 2 orders of magnitude compared to analogous glycylboronic acids, with K(i) values as low as 1 nM. On the basis of the differential binding of different analogues, the introduced carboxylate alone contributes about 2.1 kcal/mol in affinity. This carboxylate corresponds to the ubiquitous C3(4)' carboxylate of beta-lactams, and this energy represents the first thermodynamic measurement of the importance of this group in molecular recognition by class C beta-lactamases. The structures of AmpC in complex with two of these inhibitors were determined by X-ray crystallography at 1.72 and 1.83 A resolution. These structures suggest a structural basis for the high affinity of the new compounds and provide templates for further design. The highest affinity inhibitor was 5 orders of magnitude more selective for AmpC than for characteristic serine proteases, such as chymotrypsin. This inhibitor reversed the resistance of clinical pathogens to the third generation cephalosporin ceftazidime; it may serve as a lead compound for drug discovery to combat bacterial resistance to beta-lactam antibiotics.
-===AmpC beta-lactamase in complex with an m.carboxyphenylglycylboronic acid bearing the cephalothin R1 side chain===
+Nanomolar inhibitors of AmpC beta-lactamase.,Morandi F, Caselli E, Morandi S, Focia PJ, Blazquez J, Shoichet BK, Prati F J Am Chem Soc. 2003 Jan 22;125(3):685-95. PMID:12526668<ref>PMID:12526668</ref>
-{{ABSTRACT_PUBMED_12526668}}
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
-==About this Structure==
+<div class="pdbe-citations 1mxo" style="background-color:#fffaf0;"></div>
-[[1mxo]] is a 2 chain structure with sequence 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=1MXO OCA].
 ==See Also==
-*[[Beta-lactamase|Beta-lactamase]]
+*[[Beta-lactamase 3D structures|Beta-lactamase 3D structures]]
+== References ==
-==Reference==
+<references/>
-<ref group="xtra">PMID:012526668</ref><references group="xtra"/>
+__TOC__
-[[Category: Beta-lactamase]]
+</StructureSection>
 [[Category: Escherichia coli]]
-[[Category: Blazquez, J.]]
+[[Category: Large Structures]]
-[[Category: Caselli, E.]]
+[[Category: Blazquez J]]
-[[Category: Focia, P J.]]
+[[Category: Caselli E]]
-[[Category: Morandi, F.]]
+[[Category: Focia PJ]]
-[[Category: Morandi, S.]]
+[[Category: Morandi F]]
-[[Category: Prati, F.]]
+[[Category: Morandi S]]
-[[Category: Shoichet, B K.]]
+[[Category: Prati F]]
-[[Category: Ampc]]
+[[Category: Shoichet BK]]
-[[Category: Beta-lactamase]]
-[[Category: Cephalosporinase]]
-[[Category: Hydrolase]]
-[[Category: Serine hydrolase]]