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[[Image:2rcx.gif|left|200px]]
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{{STRUCTURE_2rcx|  PDB=2rcx  |  SCENE=  }}
'''AmpC Beta-lactamase in complex with (1R)-1-(2-Thiophen-2-yl-acetylamino)-1-(3-(2-carboxyvinyl)-phenyl) methylboronic acid'''


==AmpC Beta-lactamase in complex with (1R)-1-(2-Thiophen-2-yl-acetylamino)-1-(3-(2-carboxyvinyl)-phenyl) methylboronic acid==
<StructureSection load='2rcx' size='340' side='right'caption='[[2rcx]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2rcx]] 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=2RCX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2RCX 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&#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=SM4:(1R)-1-(2-THIOPHEN-2-YL-ACETYLAMINO)-1-(3-(2-CARBOXYVINYL)-PHENYL)+METHYLBORONIC+ACID'>SM4</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=2rcx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2rcx OCA], [https://pdbe.org/2rcx PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2rcx RCSB], [https://www.ebi.ac.uk/pdbsum/2rcx PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2rcx 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/rc/2rcx_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=2rcx ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Boronic acids have proved to be promising selective inhibitors of beta-lactamases, acting as transition state analogues. Starting from a previously described nanomolar inhibitor of AmpC beta-lactamase, three new inhibitors were designed to gain interactions with highly conserved residues, such as Asn343, and to bind more tightly to the enzyme. Among these, one was obtained by stereoselective synthesis and succeeded in placing its anionic group into the carboxylate binding site of the enzyme, as revealed by X-ray crystallography of the complex inhibitor/AmpC. Nevertheless, it failed at improving affinity, when compared to the lead from which it was derived. The origins of this structural and energetic discrepancy are discussed.


==Overview==
Structure-based optimization of cephalothin-analogue boronic acids as beta-lactamase inhibitors.,Morandi S, Morandi F, Caselli E, Shoichet BK, Prati F Bioorg Med Chem. 2008 Feb 1;16(3):1195-205. Epub 2007 Nov 7. PMID:17997318<ref>PMID:17997318</ref>
Boronic acids have proved to be promising selective inhibitors of beta-lactamases, acting as transition state analogues. Starting from a previously described nanomolar inhibitor of AmpC beta-lactamase, three new inhibitors were designed to gain interactions with highly conserved residues, such as Asn343, and to bind more tightly to the enzyme. Among these, one was obtained by stereoselective synthesis and succeeded in placing its anionic group into the carboxylate binding site of the enzyme, as revealed by X-ray crystallography of the complex inhibitor/AmpC. Nevertheless, it failed at improving affinity, when compared to the lead from which it was derived. The origins of this structural and energetic discrepancy are discussed.


==About this Structure==
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
2RCX is a [[Single protein]] structure of 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=2RCX OCA].
</div>
<div class="pdbe-citations 2rcx" style="background-color:#fffaf0;"></div>


==Reference==
==See Also==
Structure-based optimization of cephalothin-analogue boronic acids as beta-lactamase inhibitors., Morandi S, Morandi F, Caselli E, Shoichet BK, Prati F, Bioorg Med Chem. 2007 Nov 6;. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/17997318 17997318]
*[[Beta-lactamase 3D structures|Beta-lactamase 3D structures]]
[[Category: Beta-lactamase]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Escherichia coli]]
[[Category: Escherichia coli]]
[[Category: Single protein]]
[[Category: Large Structures]]
[[Category: Morandi, F.]]
[[Category: Morandi F]]
[[Category: Morandi, S.]]
[[Category: Morandi S]]
[[Category: Prati, F.]]
[[Category: Prati F]]
[[Category: Shoichet, B K.]]
[[Category: Shoichet BK]]
[[Category: Ampc]]
[[Category: Antibiotic resistance]]
[[Category: Beta-lactamase]]
[[Category: Cephalosporinase]]
[[Category: Periplasm]]
[[Category: Serine hydrolase]]
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Retrieved from "https://proteopedia.org/2rcx"