LacZymes - A structural view on enzymes involved in ß-lactam antibiotic resistance

Publications

  1. Fröhlich C., Gama J.A., Harms K., Hirvonen V.H.A., Lund B.A., van der Kamp M.W., Johnsen P.J., Samuelsen Ø. and Leiros H.-K.S. (2020) Cryptic β-lactamase evolution is driven by low β-lactam concentrations. bioRxiv, 2020.2012.2001.404343. First published on, doi: 10.1101/2020.12.01.404343. Submitted to mSphere, jan 2021.
  2. Leiros, H.-K.S.*, Thomassen, A. M., Samuelsen, Ø., Flach, C.-F., Kotsakis, S. D. & Larsson, D. G. J. (2020) Structural insights into the enhanced carbapenemase efficiency of OXA-655 compared to OXA-10. Febs Open Bio, 10(9):1821-1832. doi: 10.1002/2211-5463.12935.
  3. Muhammad, Z., Skagseth, S., Boomgaren, M., Akhter, S., Fröhlich, C., Ismael, A., Christopeit, T., Bayer, A. & Leiros, H.-K.S.* (2020) Structural studies of triazole inhibitors with promising inhibitor effects against antibiotic resistance metallo-β-lactamases. Bioorganic & Medicinal Chemistry. 28(15):115598. doi: 10.1016/j.bmc.2020.115598.
  4. Fröhlich, C., Sørum, V., Huber, S., Samuelsen, Ø., Berglund, F., Kristiansson, E., Kotsakis, S. D., Marathe, N. P., Larsson, D. G. J. & Leiros, H.-K.S. (2020) Structural and biochemical characterization of the environmental metallo-β-lactamases MYO-1, ECV-1 and SHD-1. J. Antimicrob. Chemother. 75(9):2554-2563. doi:10.1093/jac/dkaa175.
  5. Samuelsen, Ø., Åstrand, O. A. H., Fröhlich, C., Heikal, A., Skagseth, S., Carlsen, T. J. O., Leiros, H.-K. S., Bayer, A., Schnaars, C., Kildahl-Andersen, G., Lauksund, S., Finke, S., Huber, S., Gjøen, T., Andresen, A. M. S., Økstad, O. A. & Rongved, P. (2020) ZN148 – a modular synthetic metallo-β-lactamase inhibitor reverses carbapenem-resistance in Gram-negative pathogens in vivo. Antimicrob Agents Chemother, 64 (6), e02415-19.  AAC.02415-19. DOI:10.1128/AAC.02415-19
  6. Fröhlich, C., Sørum, V., Thomassen, A. M., Johnsen, P. J., Leiros, H.-K. S., & Samuelsen, Ø. (2019) OXA-48-Mediated Ceftazidime-Avibactam Resistance Is Associated with Evolutionary Trade-Offs. mSphere 4 (2). pii: e00024-19. doi: 10.1128/mSphere.00024-19.
  7. Prandina, A., Radix, S., Borgne, M. L., Jordheim, L. P., Bousfiha, Z., Fröhlich, C., Leiros, H.-K. S., Samuelsen, Ø., Frøvold, E., Rongved, P. & Åstrand, O. A. H. (2019) Synthesis and biological evaluation of new dipicolylamine zinc chelators as metallo-β-lactamase inhibitors, Tetrahedron, 75 (2), 1525-1540: DOI: 10.1016/j.tet.2019.02.004
  8. Lund, B. A., Thomassen, A. M., Nesheim, B. H. B., Carlsen, T. J., Isaksson, J., Christopeit, T., and Leiros, H.-K. S.* (2018) The biological assembly of OXA-48 reveal a dimer interface high charge complementarity and very high affinity, FEBS J. 285 (22), 4214-4228 doi:10.1111/febs.14643.
  9. Akhter. S., Lund, B. A., Isamel, A., Lange, M., Isaksson, J., Christopeit, T., Leiros, H.-K. S.* & Bayer, A. (2018) A focused fragment library targeting the antibiotic resistance enzyme - Oxacillinase-48: Synthesis, structural evaluation and inhibitor design., Eur J Med Chem. 145, 634-648. DOI: 10.1016/j.ejmech.2017.12.085
  10. Marcoccia, F., Leiros, H.-K. S., Aschi, M., Amicosante, G. & Perilli, M. (2018) Exploring the role of L209 residue in the active site of NDM-1 a metallo-β-lactamase, PLOS One13 (1), e0189686. DOI: 10.1371/journal.pone.0189686.
  11. Samuelsen, Ø., Hansen, F., Aasnæs, B., Hasman, H., Lund, B.A., Leiros, H.K.S.,Lilje, B., Janice, J., Jakobsen, L., Littauer, P., Søes, L.M., Holzknecht, B.J., Andersen, L.P., Stegger, M., Andersen, P.S., Hammerum, A.M. (2017). Dissemination and Characteristics of a Novel Plasmid-Encoded Carbapenem-Hydrolyzing Class D β-Lactamase, OXA-436 from Four Patients Involving Six Different Hospitals in Denmark. Antimicrob Agents Chemother. 62 (1)  pii: e01260-17.  doi: 10.1128/AAC.01260-17. 
  12. Lund, B. A., Thomassen, A. M., Nesheim, B. H. B., Carlsen, T. J., Isaksson, J., Christopeit, T., and Leiros, H.-K. S.* (2018) The biological assembly of OXA-48 reveal a dimer interface high charge complementarity and very high affinity, FEBS J. 285 (22), 4214-4228 doi:10.1111/febs.14643.
  13. Lund, B.A., Thomassen, A.M., Carlsen, T.J.O., Leiros, H.-K.S.* (2017) Structure, activity and thermostability investigations of OXA-163, OXA-181 and OXA-245 using biochemical analysis, crystal structures and differential scanning calorimetry analysis. Acta Crystallogr F Struct Biol Commun. 73(Pt 10), 579-587. doi.org/10.1107/S2053230X17013838
  14. Skagseth, S., Christopeit, T., Akhter, S., Bayer, A., Samuelsen, Ø. & Leiros, H.-K. S.*(2017) Structural insights into TMB-1 and the role of residue 119 and 228 in substrate and inhibitor binding,  Antimicrobial Agents and Chemotherapy. 61 (8), e02602-16. doi.org/10.1128/AAC.02602-16.
  15. Skagseth, S., Akhter, S., Paulsen, M.H., Muhammad, Z., Lauksund, S., Samuelsen, Ø., Leiros, H.-K. S.* & Bayer, A.*(2017) Metallo-β-lactamase inhibitors by bioisosteric replacement: preparation, activity and binding, European Journal of Medicinal Chemistry. 138, 159-173. doi.org/10.1016/j.ejmech.2017.04.035.
  16. Christopeit, T., Yang, K.-W., Yang, S.-K. & Leiros, H.-K. S.*(2016) The structure of the metallo-β-lactamase VIM-2 in complex with a triazolylthioacetamide inhibitor, Acta Crystallogr F Struct Biol Commun72, 813-819. DOI: 10.1107/S2053230X16016113.
  17. Lund, B.A., Christopeit, T., Guttormsen, Y., Bayer, A.,Leiros, H.-K.S.* (2016). Surface plasmon resonance based screening and design of inhibitor scaffolds for the antibiotic resistance enzyme OXA-48. J. Med. Chem.: 59, 5542–5554. Doi.org/10.1021/acs.jmedchem.6b00660.
  18. Christopeit, T., Albert, A., Leiros, H.-K.S.*(2016) Discovery of a novel covalent non-ß-lactam inhibitor of the metallo-ß-lactamase NDM-1, Bioorg. Med. Chem.24: 2947-53. DOI.org/10.1016/j.bmc.2016.04.064
  19. Christopeit, T.,Leiros, H.-K.S.* (2016). Fragment-based Discovery of Inhibitor Scaffolds Targeting the Metallo-ß-lactamases NDM-1 and VIM-2. Bioorg. Med. Chem. Lett. 8:1973-1977.  DOI.org/10.1016/j.bmcl.2016.03.004
  20. Skagseth, S., Carlsen, T.J., Bjerga, G.E., Spencer, J., Samuelsen, Ø.,Leiros, H.-K.S. * (2015). Investigating the role of residues W228 and Y233 in the structure and activity of the GIM-1 metallo-ß-lactamase. Role of Residues W228 and Y233 in the Structure and Activity of Metallo-ß-Lactamase GIM-1. Antimicrob. Agents. Chemother. 60, 990-1002. DOI.org/10.1128/aac.02017-15.
  21. Christopeit T., Carlsen, T.J., Helland, R.,Leiros H.-K.S.* (2015). Discovery of Novel Inhibitor Scaffolds against the Metallo-ß-lactamase VIM-2 by Surface Plasmon Resonance (SPR) Based Fragment Screening. J. Med. Chem. 58: 8671-8682. DOI.org/10.1021/acs.jmedchem.5b01289
  22. Leiros, H.-K. S.,*Edvardsen, K. S., Bjerga, G. E. K. & Samuelsen, Ø. (2015). Structural and biochemical characterization of VIM-26 show that Leu224 has implications for the substrate specificity of VIM metallo-ß-lactamases. The FEBS journal282(6), 1031-1042. DOI.org/10.1111/febs.13200
  23. Leiros, H.-K. S.*,Skagseth, S., Edvardsen, K. S. W., Lorentzen, M. S., Bjerga, G. E. K., Leiros, I. & Samuelsen, Ø. (2014) His224 Alters the R2 Drug Binding Site and Phe218 Influences the Catalytic Efficiency of the Metallo-ß-Lactamase VIM-7. Antimicrob. Agents Chemother. 58, 4826-36. DOI.org/10.1128/AAC.02735-13.
  24. Lund, B.A., Leiros, H.-K.S.& Bjerga, G.E.K. (2014) A high-throughput, restriction-free cloning strategy based on ccdB-gene replacement. Microbial Cell Factories13 (1), 38. DOI.org/10.1186/1475-2859-13-38
  25. Borra, P. S. Samuelsen, Ø Spencer, J. Walsh, T. R., Lorentzen, M.S. & Leiros, H-K.S.*(2013) Crystal structures of Pseudomonas aeruginosa GIM-1: Active site plasticity in metallo-ß-lactamases Antimicrob Agents Chemother. 57, 848-54. DOI: 10.1128/AAC.02227-12
  26. Leiros, H-K.S.,*Borrai, P.S., Brandsdal, B.O., Edvardsen, K.S., Spencer, J., Walsh, T.R. & Samuelsen Ø. (2012) Crystal structure of the mobile metallo-ß-lactamase AIM-1 from Pseudomonas aeruginosa: insights into antibiotic binding and the role of Gln157. Antimicrob. Agents Chemother. 56, 4341-4353.  DOI: 10.1128/AAC.00448-12
  27. Borra, P.S., Leiros, H.-K.S.,Ahmad, R., Spencer, J., Leiros, I., Walsh, T.R., Sundsfjord, A. & Samuelsen Ø. (2011) Structural and computational investigations of VIM-7: Insights into the substrate specificity of VIM metallo-ß-lactamases. J. Mol. Biol., 411 (1), 174-189. DOI: 10.1016/j.jmb.2011.05.035
 
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Page administrator: Hanna-Kirsti Schrøder Leiros
Last updated: 23.03.2021 15:19