View source for 5hfo


==CRYSTAL STRUCTURE OF OXA-232 BETA-LACTAMASE==
<StructureSection load='5hfo' size='340' side='right'caption='[[5hfo]], [[Resolution|resolution]] 2.21&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5hfo]] 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=5HFO OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5HFO 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]] 2.21&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=KCX:LYSINE+NZ-CARBOXYLIC+ACID'>KCX</scene>, <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=5hfo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5hfo OCA], [https://pdbe.org/5hfo PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5hfo RCSB], [https://www.ebi.ac.uk/pdbsum/5hfo PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5hfo ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/M4JTK1_ECOLX M4JTK1_ECOLX] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Increasing numbers of variants of the carbapenem-hydrolyzing class D beta-lactamase OXA-48 are identified in Enterobacterales worldwide. Among them, OXA-181 and OXA-232 are of particular interest, as they differ from each other by a single amino acid substitution at position 214 (R in OXA-181 and S in OXA-232) that results in reduced carbapenem-hydrolyzing activity for OXA-232. To investigate the role of amino acid position 214 (AA214), the X-ray structure of OXA-232 was determined and AA214 of OXA-48 and of OXA-232 was replaced by G, L, D, E, S, R, and K using site-directed mutagenesis. These mutants were phenotypically characterized, and three mutants of OXA-232 were purified to study their steady-state kinetic properties. The X-ray structure of OXA-232 along with molecular modeling studies showed that the interaction via a salt bridge between R214 and D159 in OXA-48 is not possible with the G214 or S214 mutation. In contrast, with K214, which is also positively charged, the interaction with D159 is maintained. With the E214 mutant, an alternative binding conformation of imipenem that is not compatible with a nucleophilic attack by S70 was evidenced. Thus, imipenem has a very poor apparent affinity for the E214 mutant because of its nonproductive binding mode. Similarly, we could explain the lack of temocillin hydrolysis by the OXA-232-S214E mutant, which is due to the unfavorable interaction between the negatively charged R1 substituent of temocillin with the E214 residue. Overall, we demonstrate that AA214 in OXA-48-like beta-lactamases is critical for the carbapenemase activity.

Role of Arginine 214 in the Substrate Specificity of OXA-48.,Oueslati S, Retailleau P, Marchini L, Berthault C, Dortet L, Bonnin RA, Iorga BI, Naas T Antimicrob Agents Chemother. 2020 Apr 21;64(5). pii: AAC.02329-19. doi:, 10.1128/AAC.02329-19. Print 2020 Apr 21. PMID:32071047<ref>PMID:32071047</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 5hfo" style="background-color:#fffaf0;"></div>

==See Also==
*[[Beta-lactamase 3D structures|Beta-lactamase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Escherichia coli]]
[[Category: Large Structures]]
[[Category: Cisse C]]
[[Category: Iorga B]]
[[Category: Naas T]]
[[Category: Nordmann P]]
[[Category: Oueslati S]]
[[Category: Retailleau P]]