Journal article

Characterizing the conformational dynamics of metal-free PsaA using molecular dynamics simulations and electron paramagnetic resonance spectroscopy

E Deplazes, SL Begg, JH Van Wonderen, R Campbell, B Kobe, JC Paton, F MacMillan, CA McDevitt, ML O'Mara

Biophysical Chemistry | ELSEVIER SCIENCE BV | Published : 2015

Abstract

Prokaryotic metal-ion receptor proteins, or solute-binding proteins, facilitate the acquisition of metal ions from the extracellular environment. Pneumococcal surface antigen A (PsaA) is the primary Mn2+-recruiting protein of the human pathogen Streptococcus pneumoniae and is essential for its in vivo colonization and virulence. The recently reported high-resolution structures of metal-free and metal-bound PsaA have provided the first insights into the mechanism of PsaA-facilitated metal binding. However, the conformational dynamics of metal-free PsaA in solution remain unknown. Here, we use continuous wave electron paramagnetic resonance (EPR) spectroscopy and molecular dynamics (MD) simula..

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Grants

Awarded by National Computational Infrastructure


Funding Acknowledgements

This research was undertaken with the assistance of resources provided at the NCI National Facility systems at the Australian National University through the National Computational Merit Allocation Scheme supported by the Australian Government. We thank Dr. R.M. Counago and Dr. C. Adolphe for their insights and discussions. This work was supported by the Australian Research Council (ARC) grants [DP120103957, DP150104515] to C.A.M. and J.C.P., the National Health and Medical Research Council (NHMRC) grants; [1022240, 1080784] to C.A.M., and [565526, 1071659] to J.C.P. and B.K., and the Medical Advances without Animal Trust (MAWA) to E.D. and M.L.O. The author(s) declare no competing financial interests. M.L.O. holds an ARC DECRA [DE120101550]. B.K. is a NHMRC Senior Research Fellow. J.C.P. is a NHMRC Senior Principal Research Fellow. E.D. is a NHMRC ECR Fellow and part of the work was carried out while she was on a Fellowship of the Swiss National Science Foundation.