View source for 4uwo


==Native di-zinc VIM-26. Leu224 in VIM-26 from Klebsiella pneumoniae has implications for drug binding.==
<StructureSection load='4uwo' size='340' side='right'caption='[[4uwo]], [[Resolution|resolution]] 1.56&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4uwo]] is a 1 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=4UWO OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4UWO 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]] 1.555&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=OCS:CYSTEINESULFONIC+ACID'>OCS</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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=4uwo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4uwo OCA], [https://pdbe.org/4uwo PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4uwo RCSB], [https://www.ebi.ac.uk/pdbsum/4uwo PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4uwo ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/E5BDC6_KLEPN E5BDC6_KLEPN] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
During the last decades antimicrobial resistance has become a global health problem. Metallo-beta-lactamases (MBLs) which are broad-spectrum beta-lactamases that inactivate virtually all beta-lactams including carbapenems, are contributing to this health problem. In this study a novel MBL variant, termed VIM-26, identified in a Klebsiella pneumoniae isolate was studied. VIM-26 belongs to the Verona integron-encoded metallo-beta-lactamase (VIM) family of MBLs and is a His224Leu variant of the well-characterized VIM-1 variant. In this study, we report the kinetic parameters, minimum inhibitory concentrations and crystal structures of a recombinant VIM-26 protein, and compare them to previously published data on VIM-1, VIM-2 and VIM-7. The kinetic parameters and minimum inhibitory concentration determinations show that VIM-26, like VIM-7, has higher penicillinase activity but lower cephalosporinase activity than VIM-1 and VIM-2. The four determined VIM-26 crystal structures revealed mono- and di-zinc forms, where the Zn1 ion has distorted tetrahedral coordination geometry with an additional water molecule (W2) at a distance of 2.6-3.7 A, which could be important during catalysis. The R2 drug binding site in VIM-26 is more open compared to VIM-2 and VIM-7 and neutrally charged due to Leu224 and Ser228. Thus, the VIM-26 drug binding properties are different from the VIM-2 (Tyr224/Arg228) and VIM-7 (His224/Arg228) structures, indicating a role of these residues in the substrate specificity.

Structural and biochemical characterization of VIM-26 shows that Leu224 has implications for the substrate specificity of VIM metallo-beta-lactamases.,Leiros HK, Edvardsen KS, Bjerga GE, Samuelsen O FEBS J. 2015 Jan 19. doi: 10.1111/febs.13200. PMID:25601024<ref>PMID:25601024</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4uwo" 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: Bjerga GEK]]
[[Category: Edvardsen KSW]]
[[Category: Leiros H-KS]]
[[Category: Samuelsen O]]