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== Function == | == Function == | ||
[https://www.uniprot.org/uniprot/C5HUY1_ACIBA C5HUY1_ACIBA] | [https://www.uniprot.org/uniprot/C5HUY1_ACIBA C5HUY1_ACIBA] | ||
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== Publication Abstract from PubMed == | |||
GES-1 is a class A extended-spectrum beta-lactamase conferring resistance to penicillins, first-, second-generation cephalosporins and to ceftazidime. However, GES-1 poorly hydrolyzes aztreonam and cephamycins, and exhibits very low k(cat) values for carbapenems. Twenty-two GES variants have been discovered thus far, differing from each other by 1-3 amino acid substitutions that affect substrate specificity. GES-11 possesses a Gly243Ala substitution which seems to confer this variant an increased activity against aztreonam and ceftazidime. GES-12 differs from GES-11 by a single Thr237Ala substitution while GES-14 differs from GES-11 by the Gly170Ser mutation which is known to confer increased carbapenemase activity. GES-11 and GES-12 were kinetically characterized and compared with GES-1 and GES-14. Purified GES-11 and GES-12 showed strong activities against most tested beta-lactams with the exception of temocillin, cefoxitin and carbapenems. Both variants showed a significantly increased rate of hydrolysis of cefotaxime, ceftazidime and aztreonam. On the other hand, GES-11, GES-12 (and GES-14) variants all containing Ala243 exhibited increased susceptibility to classical inhibitors. The crystallographic structures of the GES-11 and GES-14 beta-lactamases were solved. The overall structures of GES-11 and GES-14 are similar to that of GES-1. The Gly243Ala substitution caused only subtle local rearrangements, notably in the typical carbapenemase disulfide bond. The active sites of GES-14 and GES-11 are very similar, the Gly170Ser substitution leading only to the formation of additional hydrogen bonds of the Ser residue with the hydrolytic water and the Glu166 residue. | |||
Kinetic and crystallographic studies of extended spectrum GES-11, GES-12 and GES-14 beta-lactamases.,Delbruck H, Bogaerts P, Kupper MB, de Castro RR, Bennink S, Glupczynski Y, Galleni M, Hoffmann KM, Bebrone C Antimicrob Agents Chemother. 2012 Aug 20. PMID:22908160<ref>PMID:22908160</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
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==See Also== | ==See Also== | ||
*[[Beta-lactamase 3D structures|Beta-lactamase 3D structures]] | *[[Beta-lactamase 3D structures|Beta-lactamase 3D structures]] | ||
== References == | |||
<references/> | |||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||