2qpn
GES-1 beta-lactamase
Structural highlights
FunctionBLAG1_KLEPN Extended-spectrum beta-lactamase (ESBL) which confers resistance to penicillins, as well as first, second, third and fourth-generation cephalosporins (PubMed:10681329, PubMed:12936982, PubMed:19656947, PubMed:20696873, PubMed:29507065). Has ceftazidime-hydrolyzing activity (PubMed:10681329, PubMed:12936982, PubMed:19656947, PubMed:20696873, PubMed:29507065). Inactive against the carbapenems, imipenem, meropenem, ertapenem and doripenem (PubMed:10681329, PubMed:19656947, PubMed:29507065). However, weak hydrolytic activity with respect to imipenem has also been reported (PubMed:20696873).[1] [2] [3] [4] [5] Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedThe structure of the class A extended-spectrum beta-lactamase GES-1 from Klebsiella pneumoniae has been determined to 1.1 A resolution. GES-1 has the characteristic active-site disulfide bond of the carbapenemase family of beta-lactamases and has a structure that is very similar to those of other known carbapenemases, including NMC-A, SME-1 and KPC-2. Most residues implicated in the catalytic mechanism of this class of enzyme are present in the GES-1 active site, including Ser70, which forms a covalent bond with the carbonyl C atom of the beta-lactam ring of the substrate during the formation of an acyl-enzyme intermediate, Glu166, which is implicated as both the acylation and deacylation base, and Lys73, which is also implicated as the acylation base. A water molecule crucial to catalysis is observed in an identical location as in other class A beta-lactamases, interacting with the side chains of Ser70 and Glu166. One important residue, Asn170, also normally a ligand for the hydrolytic water, is missing from the GES-1 active site. This residue is a glycine in GES-1 and the enzyme is unable to hydrolyze imipenem. This points to this residue as being critically important in the hydrolysis of this class of beta-lactam substrate. This is further supported by flexible-docking studies of imipenem with in silico-generated Gly170Asn and Gly170Ser mutant GES-1 enzymes designed to mimic the active sites of imipenem-hydrolyzing point mutants GES-2 and GES-5. Structure of GES-1 at atomic resolution: insights into the evolution of carbapenamase activity in the class A extended-spectrum beta-lactamases.,Smith CA, Caccamo M, Kantardjieff KA, Vakulenko S Acta Crystallogr D Biol Crystallogr. 2007 Sep;63(Pt 9):982-92. Epub 2007, Aug 17. PMID:17704567[6] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
| ||||||||||||||||||||
