Extended-spectrum and inhibitor-resistant TEM-type beta-lactamases: mutations, specificity, and three-dimensional structure.
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TL;DR: The intent of this minireview is to help microbiologists and molecular geneticists visualize the relationship between b-lactamase mutations and three-dimensional structure.
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Abstract: In the last decade the usefulness of the oximino-b-lactams and monobactams has been compromised by the increasing presence of clinically derived extended-spectrum b-lactamases (10, 16, 40, 41, 53, 65, 74). Especially alarming are studies that describe isolates resistant to mechanism-based b-lactamase inhibitors of the clavulanate type (3, 4, 6, 62, 88). With the atomic-level detail that X-ray crystallography is now providing about the tertiary structures of the class A (or group 2) b-lactamases, it is becoming possible to rationalize how a particular amino acid change might alter the substrate profile and catalytic parameters. The intent of this minireview, therefore, is to help microbiologists and molecular geneticists visualize the relationship between b-lactamase mutations and three-dimensional structure. Although extended-spectrum b-lactamases from both chromosomal and plasmid genes are known (40, 67, 85), the focus here is on the better-characterized plasmidmediated TEM and SHV-type b-lactamases of class A.
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Citations
The Interplay of Electrostatics and Chemical Positioning in the Evolution of Antibiotic Resistance in TEM β-Lactamases
TL;DR: In this paper, a detailed kinetic analysis and the vibrational Stark effect are used to quantify the changes in rate and electric fields in the Michaelis and acyl-enzyme complexes for penicillin G and cefotaxime to ascertain the evolutionary role of electric fields to modulate function.
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The catalytic efficiency (kcat/Km) of the class A β-lactamase Toho-1 correlates with the thermal stability of its catalytic intermediate analog
Yasushi Nitanai,Tatsuro Shimamura,Takuro Uchiyama,Yoshikazu Ishii,Michiyo Takehira,Katsuhide Yutani,Hiroshi Matsuzawa,Masashi Miyano +7 more
TL;DR: A relationship exists between the kinetic parameters and the stability of the intermediates of a catalytic intermediate (analog) and its kinetic parameters, and a new method for investigating the catalytic properties of enzymes against any substrates is demonstrated.
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Characterization of a New Extended-Spectrum β-Lactamase (TEM-87) Isolated in Proteus mirabilis during an Italian Survey
Mariagrazia Perilli,Bernardetta Segatore,Maria Rosaria De Massis,Nicola Franceschini,Ciro Bianchi,G. M. Rossolini,Gianfranco Amicosante +6 more
TL;DR: Kinetic analysis of TEM-87 revealed extended-spectrum activity against oxyimino cephalosporins (preferentially ceftazidime) and aztreonam and Expression of blaTEM- 87 in Escherichia coli decreased the host susceptibility to these drugs.
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Effects of Ser130Gly and Asp240Lys Substitutions in Extended-Spectrum β-Lactamase CTX-M-9
TL;DR: In CTX-M-9 extended-spectrum β-lactamases, an S130G mutation induced a 40- to 650-fold increase in 50% inhibitory concentrations but decreased hydrolytic activity against cefotaxime, in contrast with what was observed with certain TEM/SHV-type ESBLs.
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Substitution of Thr for Ala-237 in TEM-17, TEM-12 and TEM-26: Alterations in β-lactam resistance conferred on Escherichia coli
Panagiota Giakkoupi,Panagiota Giakkoupi,Andrea M. Hujer,Vivi Miriagou,Eva Tzelepi,Robert A. Bonomo,Leonidas S. Tzouvelekis +6 more
TL;DR: Quantification of beta-lactamase activities and immunoblotting indicated that Ala-237-->Thr did not significantly affect expression levels of these extended-spectrum beta- lactamases, while introduction of Thr-237 improved activity against cefotaxime and ceftriaxone in TEM-12 and Tem-26, but not in T EM-17.
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