View source for 2qpn


==GES-1 beta-lactamase==
<StructureSection load='2qpn' size='340' side='right'caption='[[2qpn]], [[Resolution|resolution]] 1.10&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2qpn]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Klebsiella_pneumoniae Klebsiella pneumoniae]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2QPN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2QPN 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]] 1.1&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=2qpn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2qpn OCA], [https://pdbe.org/2qpn PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2qpn RCSB], [https://www.ebi.ac.uk/pdbsum/2qpn PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2qpn ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/BLAG1_KLEPN BLAG1_KLEPN] Extended-spectrum beta-lactamase (ESBL) which confers resistance to penicillins, as well as first, second, third and fourth-generation cephalosporins (PubMed:10681329, PubMed:12936982, PubMed:19656947, PubMed:20696873, PubMed:29507065). Has ceftazidime-hydrolyzing activity (PubMed:10681329, PubMed:12936982, PubMed:19656947, PubMed:20696873, PubMed:29507065). Inactive against the carbapenems, imipenem, meropenem, ertapenem and doripenem (PubMed:10681329, PubMed:19656947, PubMed:29507065). However, weak hydrolytic activity with respect to imipenem has also been reported (PubMed:20696873).<ref>PMID:10681329</ref> <ref>PMID:12936982</ref> <ref>PMID:19656947</ref> <ref>PMID:20696873</ref> <ref>PMID:29507065</ref> 
== 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/qp/2qpn_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=2qpn ConSurf].
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== Publication Abstract from PubMed ==
The structure of the class A extended-spectrum beta-lactamase GES-1 from Klebsiella pneumoniae has been determined to 1.1 A resolution. GES-1 has the characteristic active-site disulfide bond of the carbapenemase family of beta-lactamases and has a structure that is very similar to those of other known carbapenemases, including NMC-A, SME-1 and KPC-2. Most residues implicated in the catalytic mechanism of this class of enzyme are present in the GES-1 active site, including Ser70, which forms a covalent bond with the carbonyl C atom of the beta-lactam ring of the substrate during the formation of an acyl-enzyme intermediate, Glu166, which is implicated as both the acylation and deacylation base, and Lys73, which is also implicated as the acylation base. A water molecule crucial to catalysis is observed in an identical location as in other class A beta-lactamases, interacting with the side chains of Ser70 and Glu166. One important residue, Asn170, also normally a ligand for the hydrolytic water, is missing from the GES-1 active site. This residue is a glycine in GES-1 and the enzyme is unable to hydrolyze imipenem. This points to this residue as being critically important in the hydrolysis of this class of beta-lactam substrate. This is further supported by flexible-docking studies of imipenem with in silico-generated Gly170Asn and Gly170Ser mutant GES-1 enzymes designed to mimic the active sites of imipenem-hydrolyzing point mutants GES-2 and GES-5.

Structure of GES-1 at atomic resolution: insights into the evolution of carbapenamase activity in the class A extended-spectrum beta-lactamases.,Smith CA, Caccamo M, Kantardjieff KA, Vakulenko S Acta Crystallogr D Biol Crystallogr. 2007 Sep;63(Pt 9):982-92. Epub 2007, Aug 17. PMID:17704567<ref>PMID:17704567</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 2qpn" style="background-color:#fffaf0;"></div>

==See Also==
*[[Beta-lactamase 3D structures|Beta-lactamase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Klebsiella pneumoniae]]
[[Category: Large Structures]]
[[Category: Caccamo M]]
[[Category: Kantardjieff KA]]
[[Category: Smith CA]]
[[Category: Vakulenko S]]