Kinetic and Structural Requirements for Carbapenemase Activity in GES-Type β-Lactamases

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Kinetic and Structural Requirements for Carbapenemase Activity in GES-Type β-Lactamases

Carbapenems are the last resort antibiotics for treatment of life-threatening infections. The GES β-lactamases are important contributors to carbapenem resistance in clinical bacterial pathogens. A single amino acid difference at position 170 of the GES-1, GES-2, and GES-5 enzymes is responsible for the expansion of their substrate profile to include carbapenem antibiotics. This highlights the ...

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Kinetic and crystallographic studies of extended-spectrum GES-11, GES-12, and GES-14 β-lactamases.

GES-1 is a class A extended-spectrum β-lactamase conferring resistance to penicillins, narrow- and expanded-spectrum cephalosporins, and 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 to 3 amino acid substitutions that affect substra...

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Nomenclature of GES-Type Extended-Spectrum -Lactamases

In two recently published articles, Wachino et al. designated a novel ceftazidime-hydrolyzing class A extended-spectrum -lactamase (ESBL) (GES-a) as GES-3 (4), and a new cephamycin-hydrolyzing and inhibitor-resistant class A ESBL (GESb) as GES-4 (5). In actuality, their articles are fraught with misleading nomenclature of GES-type ESBLs and controvertible conclusions on the relationship between...

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QM/MM simulations as an assay for carbapenemase activity in class A β-lactamases.

Carbapenems, 'last resort' antibiotics for many bacterial infections, can now be broken down by several class A β-lactamases (i.e. carbapenemases). Here, carbapenemase activity is predicted through QM/MM dynamics simulations of acyl-enzyme deacylation, requiring only the 3D structure of the apo-enzyme. This may assist in anticipating resistance and future antibiotic design.

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A plasmid-encoded class 1 integron contains GES-type extended-spectrum β-lactamases in Enterobacteriaceae clinical isolates in Mexico.

Plasmid-located extended-spectrum-lactamase (ESBL) genes are mostly found in Enterobacteriaceae (6). A new class A ESBL was identified in Klebsiella pneumoniae. It was named GES-1, and it corresponds to the ceftazidime-hydrolyzing enzyme (8). GES-type ESBLs have emerged in a variety of countries, and there are 18 known variants (http://www.lahey.org/Studies/). In the present study, we investiga...

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ژورنال

عنوان ژورنال: Biochemistry

سال: 2014

ISSN: 0006-2960,1520-4995

DOI: 10.1021/bi501052t