View source for 4yin


==Crystal structure of the extended-spectrum beta-lactamase OXA-145==
<StructureSection load='4yin' size='340' side='right'caption='[[4yin]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4yin]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Pseudomonas_aeruginosa Pseudomonas aeruginosa]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4YIN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4YIN 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]] 2.3&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FLC:CITRATE+ANION'>FLC</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=4yin FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4yin OCA], [https://pdbe.org/4yin PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4yin RCSB], [https://www.ebi.ac.uk/pdbsum/4yin PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4yin ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/C0LZL5_PSEAI C0LZL5_PSEAI] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
OBJECTIVES: We previously described extended-spectrum oxacillinase OXA-145 from Pseudomonas aeruginosa, which differs from narrow-spectrum OXA-35 by loss of Leu-155. The deletion results in loss of benzylpenicillin hydrolysis and acquisition of activity against ceftazidime. We report the crystal structure of OXA-145 and provide the basis of its switch in substrate specificity. METHODS: OXA-145 variants were generated by site-directed mutagenesis and purified to homogeneity. The crystal structure of OXA-145 was determined and molecular dynamics simulations were performed. Kinetic parameters were investigated in the absence and in the presence of sodium hydrogen carbonate (NaHCO3) for representative substrates. RESULTS: The structure of OXA-145 was obtained at a resolution of 2.3 A and its superposition with that of OXA-10 showed that Trp-154 was shifted by 1.8 A away from the catalytic Lys-70, which was not N-carboxylated. Addition of NaHCO3 significantly increased the catalytic efficiency against penicillins, but not against ceftazidime. The active-site cavity of OXA-145 was larger than that of OXA-10, which may favour the accommodation of large molecules such as ceftazidime. Molecular dynamics simulations of OXA-145 in complex with ceftazidime revealed two highly coordinated water molecules on the alpha- or beta-face of the acyl ester bond, between Ser-67 and ceftazidime, which could be involved in the catalytic process. CONCLUSIONS: Deletion of Leu-155 resulted in inefficient positioning of Trp-154, leading to a non-carboxylated Lys-70 and thus to loss of hydrolysis of the penicillins. Ceftazidime hydrolysis could be attributed to enlargement of the active site and to a catalytic mechanism independent of the carboxylated Lys-70.

Structural insights into the loss of penicillinase and the gain of ceftazidimase activities by OXA-145 beta-lactamase in Pseudomonas aeruginosa.,Meziane-Cherif D, Bonnet R, Haouz A, Courvalin P J Antimicrob Chemother. 2016 Feb;71(2):395-402. doi: 10.1093/jac/dkv375. Epub, 2015 Nov 14. PMID:26568564<ref>PMID:26568564</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4yin" style="background-color:#fffaf0;"></div>

==See Also==
*[[Beta-lactamase 3D structures|Beta-lactamase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Pseudomonas aeruginosa]]
[[Category: Bonnet R]]
[[Category: Courvalin P]]
[[Category: Haouz A]]
[[Category: Meziane-Cherif D]]