Class A β-lactamases and inhibitors: In silico analysis of the binding mode and the relationship with resistance

Journal of Biotechnology
Rebeca PereiraHelena Carla Castro

Abstract

β-lactams are one of the most common antimicrobials used to treat bacterial infections. However, bacterial resistance has compromised their efficacy, mainly due to the β-lactamase enzyme production. To overcome this resistance, β-lactamase inhibitors can be used in association with these antimicrobials. Herein, we analyzed the structural characteristics of β-lactamases and their interactions with classical inhibitors, such as clavulanic acid (CA), sulbactam (SB) and tazobactam (TZ) to gain insights into resistance. The homology models of five class A β-lactamases, namely CARB-3, IMI-1, SFO-1, SHV-5 and TEM-10, were constructed and validated and revealed an overall 3D structural conservation, but with significant differences in the electrostatic potential maps, especially at important regions in the catalytic site. Molecular dockings of CA, SB and TZ with these enzymes revealed a covalent bond with the S70 in all complexes, except Carb-3 which is in agreement with experimental data reported so far. This is likely related to the less voluminous active site of Carb-3 model. Although few specific contacts were observed in the β-lactamase-inhibitor complexes, all compounds interacted with the residues in positions 73, 130, 132, 236 ...Continue Reading

References

Mar 5, 1992·Nature·R LüthyD Eisenberg
May 15, 1991·The Biochemical Journal·R P AmblerS G Waley
Jun 1, 1982·Proceedings of the National Academy of Sciences of the United States of America·P K WeinerP A Kollman
Apr 1, 1993·Antimicrobial Agents and Chemotherapy·K BushY Yang
May 23, 1996·Nature·R W HooftE E Abola
Sep 1, 1996·Antimicrobial Agents and Chemotherapy·B A RasmussenA A Medeiros
Jan 30, 1999·Antimicrobial Agents and Chemotherapy·Y Matsumoto, M Inoue
Oct 20, 1999·International Journal of Antimicrobial Agents·J D Williams
Dec 11, 1999·Nucleic Acids Research·H M BermanP E Bourne
Jul 14, 2001·Antimicrobial Agents and Chemotherapy·R BonnetJ Sirot
Aug 23, 2001·Proceedings of the National Academy of Sciences of the United States of America·N A BakerJ A McCammon
Jan 31, 2003·Proteins·Simon C LovellDavid C Richardson
Nov 23, 2005·Bioinformatics·Konstantin ArnoldTorsten Schwede
May 23, 2007·Nucleic Acids Research·Markus Wiederstein, Manfred J Sippl
Jun 28, 2007·The Journal of Antimicrobial Chemotherapy·Jan Walther-Rasmussen, Niels Høiby
Sep 12, 2007·Bioinformatics·M A LarkinD G Higgins
Dec 25, 2007·Clinical Microbiology and Infection : the Official Publication of the European Society of Clinical Microbiology and Infectious Diseases·M Gniadkowski
Dec 25, 2007·Clinical Microbiology and Infection : the Official Publication of the European Society of Clinical Microbiology and Infectious Diseases·M Akova
May 9, 2008·Nucleic Acids Research·Christian ColeGeoffrey J Barton
Dec 10, 2009·Antimicrobial Agents and Chemotherapy·Karen Bush, George A Jacoby
Jan 13, 2010·Clinical Microbiology Reviews·Sarah M Drawz, Robert A Bonomo
Apr 13, 2010·Research in Microbiology·Kênia Valéria dos SantosLuiz de Macêdo Farias
Apr 28, 2010·Antimicrobial Agents and Chemotherapy·Krisztina M Papp-WallaceRobert A Bonomo
May 5, 2010·Nucleic Acids Research·Mickael GoujonRodrigo Lopez
Nov 17, 2010·Antimicrobial Agents and Chemotherapy·Akiko Shimizu-IbukaHiroshi Matsuzawa
Mar 12, 2011·Bioorganic & Medicinal Chemistry Letters·Yi XiaJacob J Plattner
May 17, 2012·Journal of Chemical Information and Modeling·John J IrwinRyan G Coleman
May 29, 2012·International Journal of Antimicrobial Agents·Rémy A BonninPatrice Nordmann
Jul 10, 2012·The Journal of Antimicrobial Chemotherapy·Pablo PowerEric Sauvage
Jan 26, 2013·Annals of the New York Academy of Sciences·David M Shlaes
May 17, 2013·Nucleic Acids Research·Xuchang OuyangChee Keong Kwoh
Sep 18, 2013·International Journal of Antimicrobial Agents·Syamhanin AdnanJason A Roberts

❮ Previous
Next ❯

Citations

Aug 30, 2021·Proteins·Silvia GervasoniAdrian J Mulholland

❮ Previous
Next ❯

Related Concepts

Related Feeds

Beta-lactamase Inhibitors

Beta-lactamase inhibitors are a class of antibiotics that inhibit beta-lactamases, a family of enzymes involved in bacterial resistance to beta-lactam antibiotics. Here is the latest research.

Bacterial Protein Structures

Bacterial protein structures can expedite the development of novel antibiotics. Here is the latest research on bacterial proteins and the resolution of their structures.

Beta-lactamase Inhibitors (ASM)

Beta-lactamase inhibitors are a class of antibiotics that inhibit beta-lactamases, a family of enzymes involved in bacterial resistance to beta-lactam antibiotics. Here is the latest research.

Bacterial Protein Structures (ASM)

Bacterial protein structures can expedite the development of novel antibiotics. Here is the latest research on bacterial proteins and the resolution of their structures.