View source for 2q9n


==4-Substituted Trinems as Broad Spectrum-Lactamase Inhibitors: Structure-based Design, Synthesis and Biological Activity==
<StructureSection load='2q9n' size='340' side='right'caption='[[2q9n]], [[Resolution|resolution]] 2.20&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2q9n]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Enterobacter_cloacae Enterobacter cloacae]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2Q9N OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2Q9N 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]] 2.2&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=LK5:(1S,4R,7AR)-4-BUTOXY-1-[(1R)-1-FORMYLPROPYL]-2,4,5,6,7,7A-HEXAHYDRO-1H-ISOINDOLE-3-CARBOXYLIC+ACID'>LK5</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=2q9n FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2q9n OCA], [https://pdbe.org/2q9n PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2q9n RCSB], [https://www.ebi.ac.uk/pdbsum/2q9n PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2q9n ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/AMPC_ENTCL AMPC_ENTCL] 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/q9/2q9n_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=2q9n ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
A wide variety of pathogens have acquired antimicrobial resistance as an inevitable evolutionary response to the extensive use of antibacterial agents. In particular, one of the most widely used antibiotic structural classes is the beta-lactams, in which the most common and the most efficient mechanism of bacterial resistance is the synthesis of beta-lactamases. Class C beta-lactamase enzymes are primarily cephalosporinases, mostly chromosomally encoded, and are inducible by exposure to some beta-lactam agents and resistant to inhibition by marketed beta-lactamase inhibitors. In an ongoing effort to alleviate this problem a series of novel 4-substituted trinems was designed and synthesized. Significant in vitro inhibitory activity was measured against the bacterial beta-lactamases of class C and additionally against class A. The lead compound LK-157 was shown to be a potent mechanism-based inactivator. Acylation of the active site Ser 64 of the class C enzyme beta-lactamase was observed in the solved crystal structures of two inhibitors complexes to AmpC enzyme from E. cloacae. Structure-activity relationships in the series reveal the importance of the trinem scaffold for inhibitory activity and the interesting potential of the series for further development.

4-Substituted trinems as broad spectrum beta-lactamase inhibitors: structure-based design, synthesis, and biological activity.,Plantan I, Selic L, Mesar T, Anderluh PS, Oblak M, Prezelj A, Hesse L, Andrejasic M, Vilar M, Turk D, Kocijan A, Prevec T, Vilfan G, Kocjan D, Copar A, Urleb U, Solmajer T J Med Chem. 2007 Aug 23;50(17):4113-21. Epub 2007 Aug 1. PMID:17665896<ref>PMID:17665896</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 2q9n" style="background-color:#fffaf0;"></div>

==See Also==
*[[Beta-lactamase 3D structures|Beta-lactamase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Enterobacter cloacae]]
[[Category: Large Structures]]
[[Category: Andrejasic M]]
[[Category: Copar A]]
[[Category: Hesse L]]
[[Category: Kocijan A]]
[[Category: Kocjan D]]
[[Category: Mesar T]]
[[Category: Oblak M]]
[[Category: Plantan I]]
[[Category: Prevec T]]
[[Category: Prezelj A]]
[[Category: Selic L]]
[[Category: Solmajer T]]
[[Category: Stefanic Anderluh P]]
[[Category: Turk D]]
[[Category: Urleb U]]
[[Category: Vilar M]]
[[Category: Vilfan G]]