The biological assembly of OXA-48 reveals a dimer interface with high charge complementarity and very high affinity

The FEBS Journal
Bjarte Aarmo LundHanna-Kirsti S Leiros

Abstract

Many class D β-lactamases form dimers in solution. The functional basis of the dimerization of OXA-48-like class D β-lactamases is not known, but in order to understand the structural requirements for dimerization of OXA-48, we have characterized the dimer interface. Size exclusion chromatography, small angle X-ray scattering (SAXS), and nuclear magnetic resonance (NMR) were used to confirm the oligomeric state of OXA-48 in solution. X-ray crystallographic structures were used to elucidate the key interactions of dimerization. In silico residue scanning combined with site-directed mutagenesis was used to probe hot spots of dimerization. The affinity of dimerization was quantified using microscale thermophoresis, and the overall thermostability was investigated using differential scanning calorimetry. OXA-48 was consistently found to be a dimer in solution regardless of the method used, and the biological assembly found from the SAXS envelope is consistent with the dimer identified from the crystal structures. The buried chloride that interacts with Arg206 and Arg206' at the dimer interface was found to enhance the thermal stability by > 4 °C and crystal structures and mutations (R189A, R189A/R206A) identified several additional...Continue Reading

References

Feb 9, 1976·Biochemical and Biophysical Research Communications·J W Dale, J T Smith
Sep 1, 1991·Journal of Bacteriology·C A ZijderveldN Nanninga
Jan 1, 1995·Progress in Biophysics and Molecular Biology·S Jones, J M Thornton
Dec 1, 1994·Protein Science : a Publication of the Protein Society·K E Neet, D E Timm
Oct 4, 2000·Nature Structural Biology·M PaetzelN C Strynadka
Mar 21, 2001·Biochimica Et Biophysica Acta·F DanelD M Livermore
Jun 30, 2001·Journal of Biomolecular NMR·J MarleyC Bracken
Nov 29, 2001·Proceedings of the National Academy of Sciences of the United States of America·D GolemiS Mobashery
Jun 12, 2002·Journal of Bacteriology·Xavier CharpentierJean-Michel Masson
Dec 21, 2002·Protein Science : a Publication of the Protein Society·Tao SunJames R Knox
Apr 3, 2004·Nature Reviews. Drug Discovery·Michelle R Arkin, James A Wells
Oct 27, 2004·Trends in Biochemical Sciences·Neelan J MarianayagamJacqueline M Matthews
Dec 8, 2004·Current Opinion in Structural Biology·Jeanne A Hardy, James A Wells
Mar 22, 2007·Proceedings of the National Academy of Sciences of the United States of America·Elena SantillanaAntonio Romero
Aug 8, 2007·Journal of Molecular Biology·Evgeny Krissinel, Kim Henrick
Sep 25, 2008·Quarterly Reviews of Biophysics·Joël JaninPinak Chakrabarti
Sep 2, 2009·Antimicrobial Agents and Chemotherapy·Laurent PoirelPatrice Nordmann
Feb 4, 2010·Acta Crystallographica. Section D, Biological Crystallography·Wolfgang Kabsch
Apr 13, 2010·Acta Crystallographica. Section D, Biological Crystallography·P EmsleyK Cowtan
Apr 14, 2012·The Journal of Antimicrobial Chemotherapy·Laurent PoirelPatrice Nordmann
Apr 17, 2012·Acta Crystallographica. Section D, Biological Crystallography·Pavel V AfoninePaul D Adams
Dec 4, 2012·Nucleic Acids Research·Marie Jeanne BassePhilippe Roche
Dec 29, 2012·Methods : a Companion to Methods in Enzymology·Susanne A I SeidelStefan Duhr
Jun 15, 2013·Journal of Synchrotron Radiation·Petra PernotSean McSweeney
Jun 26, 2013·Acta Crystallographica. Section D, Biological Crystallography·Philip R Evans, Garib N Murshudov
Jul 6, 2013·Journal of Infection and Chemotherapy : Official Journal of the Japan Society of Chemotherapy·Karen Bush
May 13, 2014·Protein Engineering, Design & Selection : PEDS·Noeris K SalamDavid A Pearlman
Jun 11, 2014·Antimicrobial Agents and Chemotherapy·Hanna-Kirsti S LeirosØrjan Samuelsen
Feb 19, 2015·Antimicrobial Agents and Chemotherapy·Marisa L WinklerRobert A Bonomo
Jan 1, 2014·BMC Structural Biology·Oliviero Carugo
May 22, 2016·Infectious Disease Clinics of North America·Krisztina M Papp-Wallace, Robert A Bonomo
Jul 13, 2016·Antimicrobial Agents and Chemotherapy·Martine I AbboudJean-Marie Frère
Apr 10, 2015·ACS Infectious Diseases·Dustin T KingNatalie C J Strynadka
Dec 3, 2016·The Journal of Biological Chemistry·Dustin T KingNatalie C J Strynadka

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Citations

Jul 31, 2019·Antimicrobial Agents and Chemotherapy·Clyde A SmithSergei B Vakulenko
Sep 3, 2020·International Journal of Molecular Sciences·Evgeny P BarykinAlexander A Makarov
Jan 1, 2021·The Journal of Antimicrobial Chemotherapy·Eun-Jeong Yoon, Seok Hoon Jeong
Sep 3, 2021·Acta Crystallographica. Section F, Structural Biology Communications·Bjarte Aarmo LundHanna Kirsti Schrøder Leiros

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