View source for 4pma


==Crystal structure of CTX-M-14 S70G:S237A:R276A beta-lactamase at 1.39 Angstroms resolution==
<StructureSection load='4pma' size='340' side='right'caption='[[4pma]], [[Resolution|resolution]] 1.40&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4pma]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Klebsiella_pneumoniae_subsp._pneumoniae_HS11286 Klebsiella pneumoniae subsp. pneumoniae HS11286]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4PMA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4PMA 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]] 1.399&#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=4pma FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4pma OCA], [https://pdbe.org/4pma PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4pma RCSB], [https://www.ebi.ac.uk/pdbsum/4pma PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4pma ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/A0A0H3H219_KLEPH A0A0H3H219_KLEPH] 
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== Publication Abstract from PubMed ==
Extended-spectrum beta-lactamases (ESBLs) pose a threat to public health because of their ability to confer resistance to extended-spectrum cephalosporins such as cefotaxime. The CTX-M beta-lactamases are the most widespread ESBL enzymes among antibiotic resistant bacteria. Many of the active site residues are conserved between the CTX-M family and non-ESBL beta-lactamases such as TEM-1, but the residues Ser237 and Arg276 are specific to the CTX-M family, suggesting that they may help to define the increased specificity for cefotaxime hydrolysis. To test this hypothesis, site-directed mutagenesis of these positions was performed in the CTX-M-14 beta-lactamase. Substitutions of Ser237 and Arg276 with their TEM-1 counterparts, Ala237 and Asn276, had a modest effect on cefotaxime hydrolysis, as did removal of the Arg276 side chain in an R276A mutant. The S237A:R276N and S237A:R276A double mutants, however, exhibited 29- and 14-fold losses in catalytic efficiency for cefotaxime hydrolysis, respectively, while the catalytic efficiency for benzylpenicillin hydrolysis was unchanged. Therefore, together, the Ser237 and Arg276 residues are important contributors to the cefotaximase substrate profile of the enzyme. High-resolution crystal structures of the CTX-M-14 S70G, S70G:S237A, and S70G:S237A:R276A variants alone and in complex with cefotaxime show that residues Ser237 and Arg276 in the wild-type enzyme promote the expansion of the active site to accommodate cefotaxime and favor a conformation of cefotaxime that allows optimal contacts between the enzyme and substrate. The conservation of these residues, linked to their effects on structure and catalysis, imply that their coevolution is an important specificity determinant in the CTX-M family.

Molecular Basis for the Catalytic Specificity of the CTX-M Extended-Spectrum beta-Lactamases.,Adamski CJ, Cardenas AM, Brown NG, Horton LB, Sankaran B, Prasad BV, Gilbert HF, Palzkill T Biochemistry. 2015 Jan 20;54(2):447-57. doi: 10.1021/bi501195g. Epub 2014 Dec 24. PMID:25489790<ref>PMID:25489790</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 4pma" style="background-color:#fffaf0;"></div>

==See Also==
*[[Beta-lactamase 3D structures|Beta-lactamase 3D structures]]
== References ==
<references/>
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</StructureSection>
[[Category: Klebsiella pneumoniae subsp. pneumoniae HS11286]]
[[Category: Large Structures]]
[[Category: Adamski CJ]]
[[Category: Brown NG]]
[[Category: Cardenas AM]]
[[Category: Horton LB]]
[[Category: Palzkill T]]
[[Category: Sankaran B]]