Role of changes in the L3 loop of the active site in the evolution of enzymatic activity of VIM-type metallo-beta-lactamases

The Journal of Antimicrobial Chemotherapy
María MerinoGermán Bou

Abstract

The new metallo-beta-lactamase VIM-13 has been recently characterized. In comparison with the VIM-1 enzyme, VIM-13 showed 19 amino acid differences, 2 of which were located in the active site centre. The main objective of the present study was to assess whether differences between VIM-1 and VIM-13 beta-lactamases in the active site, at His224Leu and Ser228Arg, are necessary and sufficient to explain the microbiological and biochemical differences between the two enzymes. Single mutants VIM-13 (Leu224His) and VIM-13 (Arg228Ser) and double mutant VIM-13 (Leu224His, Arg228Ser) were created by site-directed mutagenesis with the bla(VIM-13) gene as template. VIM-1, VIM-13 and VIM-13 (Leu224His, Arg228Ser) were purified by affinity chromatography, and kinetic parameters for these enzymes were obtained with ceftazidime, cefepime and ampicillin. Ceftazidime and cefepime MICs (mg/L) for Escherichia coli TG1 expressing VIM-1, VIM-13, VIM-13 (Leu224His), VIM-13 (Arg228Ser) and VIM-13 (Leu224His, Arg228Ser) were >256 and 64, 6 and 4, 8 and 1, >256 and 8, and >256 and 48, respectively. VIM-1, VIM-13 and VIM-13 (Leu224His, Arg228Ser) revealed k(cat)/K(m) values (M(-1)s(-1)) for ceftazidime of 3.7 E(4), 1.9 E(4) and 10 E(4), respectively, and...Continue Reading

References

May 16, 1980·Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences·R P Ambler
Oct 19, 2000·Antimicrobial Agents and Chemotherapy·N FranceschiniG M Rossolini
Feb 22, 2001·Antimicrobial Agents and Chemotherapy·M GalleniUNKNOWN Metallo-beta-lactamases Working Group
Feb 4, 2003·The Journal of Antimicrobial Chemotherapy·Jean-Denis DocquierGian Maria Rossolini
Apr 16, 2005·Clinical Microbiology Reviews·Timothy R WalshPatrice Nordmann
Sep 29, 2005·Antimicrobial Agents and Chemotherapy·Gulcin G GacarHaluk Vahaboglu
Nov 24, 2005·Antimicrobial Agents and Chemotherapy·Spyros PournarasAthanassios Tsakris
Oct 18, 2006·Accounts of Chemical Research·Michael W CrowderAlejandro J Vila
Oct 12, 2007·Future Microbiology·Laurent PoirelPatrice Nordmann
Mar 26, 2008·Antimicrobial Agents and Chemotherapy·Patricia MarchiaroAlejandro J Vila
Jun 19, 2008·Antimicrobial Agents and Chemotherapy·Ørjan SamuelsenJames Spencer
Sep 4, 2008·Antimicrobial Agents and Chemotherapy·Jun-ichiro SekiguchiTeruo Kirikae
Sep 15, 2009·Current Medicinal Chemistry·Francisco J Pérez-Llarena, Germán Bou
Nov 18, 2009·Antimicrobial Agents and Chemotherapy·Jose-Manuel Rodriguez-MartinezLaurent Poirel
Dec 10, 2009·Antimicrobial Agents and Chemotherapy·Karen Bush, George A Jacoby

❮ Previous
Next ❯

Citations

Oct 28, 2011·Biochemistry·Pei W ThomasWalter Fast
Oct 22, 2010·The Journal of Antimicrobial Chemotherapy·Mariana CastanheiraRayo Morfin-Otero
Sep 8, 2011·Antimicrobial Agents and Chemotherapy·Nicholas G BrownTimothy Palzkill
Jun 7, 2012·Antimicrobial Agents and Chemotherapy·Francisco José Pérez-LlarenaGermán Bou
Jul 19, 2013·Future Medicinal Chemistry·Dustin T King, Natalie C J Strynadka
Oct 21, 2015·Antimicrobial Agents and Chemotherapy·Jürgen BremChristopher J Schofield
Dec 17, 2015·Antimicrobial Agents and Chemotherapy·Anne MakenaChristopher J Schofield
Jun 1, 2017·Antimicrobial Agents and Chemotherapy·Susann SkagsethHanna-Kirsti S Leiros
May 10, 2018·MBio·Laura Martínez-GarcíaJuan Carlos Galán
Aug 10, 2021·Antimicrobial Agents and Chemotherapy·Marie de BarsyPierre Bogaerts
May 21, 2011·Clinical Microbiology and Infection : the Official Publication of the European Society of Clinical Microbiology and Infectious Diseases·Ø SamuelsenC G Giske

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.