View source for 8iso


==Crystal structure of extended-spectrum class A beta-lactamase, CESS-1==
<StructureSection load='8iso' size='340' side='right'caption='[[8iso]], [[Resolution|resolution]] 1.29&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[8iso]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Stenotrophomonas_sp._KCTC_12332 Stenotrophomonas sp. KCTC 12332]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8ISO OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8ISO 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]] 1.29&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=PG5:1-METHOXY-2-[2-(2-METHOXY-ETHOXY]-ETHANE'>PG5</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=8iso FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8iso OCA], [https://pdbe.org/8iso PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8iso RCSB], [https://www.ebi.ac.uk/pdbsum/8iso PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8iso ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/A0A126NGE0_9GAMM A0A126NGE0_9GAMM] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
OBJECTIVES: Stenotrophomonas spp. intrinsically resistant to many beta-lactam antibiotics are found throughout the environment. CESS-1 identified in Stenotrophomonas sp. KCTC 12332 is an uncharacterized class A beta-lactamase. The goal of this study was to reveal biochemical and structural characteristics of CESS-1. METHODS: The hydrolytic activities of CESS-1 towards penicillins (penicillin G and ampicillin), cephalosporins (cephalexin, cefaclor, and cefotaxime), and carbapenems (imipenem and meropenem) was spectrophotometrically monitored. Structural information on E166Q mutants of CESS-1 acylated by cefaclor, cephalexin, or ampicillin were determined by X-ray crystallography. RESULTS: CESS-1 displayed hydrolytic activities toward penicillins and cephalosporins, with negligible activity toward carbapenems. Although cefaclor, cephalexin, and ampicillin have similar structures with identical R1 side chains, the catalytic parameters of CESS-1 toward them were distinct. The k(cat) values for cefaclor, cephalexin, and ampicillin were 1249.6 s(-1), 204.3 s(-1), and 69.8 s(-1), respectively, with the accompanying K(M) values of 287.6 muM, 236.7 muM, and 28.8 muM, respectively. CONCLUSIONS: CESS-1 was able to discriminate between cefaclor and cephalexin with a single structural difference at C3 position: -Cl (cefaclor) and -CH(3) (cephalexin). Structural comparisons among three E166Q mutants of CESS-1 acylated by cefaclor, cephalexin, or ampicillin, revealed that cooperative positional changes in the R1 side chain of substrates and their interaction with the beta5-beta6 loop affect the distance between Asn170 and the deacylating water at the acyl-enzyme intermediate state. This is directly associated with the differential hydrolytic activities of CESS-1 toward the three structurally similar beta-lactam antibiotics.

Characterization of the extended substrate spectrum of the class A beta-lactamase CESS-1 from Stenotrophomonas sp. and structure-based investigation into its substrate preference.,Jeong BG, Kim MY, Jeong CS, Do H, Hwang J, Lee JH, Cha SS Int J Antimicrob Agents. 2024 Apr 7;63(6):107171. doi: , 10.1016/j.ijantimicag.2024.107171. PMID:38588869<ref>PMID:38588869</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 8iso" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Stenotrophomonas sp. KCTC 12332]]
[[Category: Cha SS]]
[[Category: Do HW]]
[[Category: Jeong BG]]
[[Category: Jeong CS]]
[[Category: Kim MY]]
[[Category: Lee JH]]