8isp: Difference between revisions
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==Crystal structure of extended-spectrum class A beta-lactamase, CESS-1 E166Q acylated by cephalexin== | |||
<StructureSection load='8isp' size='340' side='right'caption='[[8isp]], [[Resolution|resolution]] 2.11Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[8isp]] 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=8ISP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8ISP 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]] 2.11Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=Q53:(2~{R})-2-[(1~{R})-1-[[(2~{R})-2-azanyl-2-phenyl-ethanoyl]amino]-2-oxidanyl-2-oxidanylidene-ethyl]-5-methyl-3,6-dihydro-2~{H}-1,3-thiazine-4-carboxylic+acid'>Q53</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=8isp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8isp OCA], [https://pdbe.org/8isp PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8isp RCSB], [https://www.ebi.ac.uk/pdbsum/8isp PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8isp ProSAT]</span></td></tr> | |||
</table> | |||
<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®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
<div class="pdbe-citations 8isp" 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]] | |||
Latest revision as of 12:44, 17 October 2024
Crystal structure of extended-spectrum class A beta-lactamase, CESS-1 E166Q acylated by cephalexinCrystal structure of extended-spectrum class A beta-lactamase, CESS-1 E166Q acylated by cephalexin
Structural highlights
Publication Abstract from PubMedOBJECTIVES: 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[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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