a molecular mechanism for bacterial susceptibility to zinc细菌对锌的易感性的分子机制.pdfVIP

A Molecular Mechanism for Bacterial Susceptibility to Zinc 1 1 2 3 2 Christopher A. McDevitt , Abiodun D. Ogunniyi , Eugene Valkov , Michael C. Lawrence , Bostjan Kobe , 2 1 Alastair G. McEwan , James C. Paton * 1 Research Centre for Infectious Diseases, School of Molecular and Biomedical Science, University of Adelaide, Adelaide, South Australia, Australia, 2 School of Chemistry and Molecular Biosciences, Australian Infectious Diseases Research Centre and Institute for Molecular Bioscience, University of Queensland, Brisbane, Australia, 3 The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia Abstract Transition row metal ions are both essential and toxic to microorganisms. Zinc in excess has significant toxicity to bacteria, and host release of Zn(II) at mucosal surfaces is an important innate defence mechanism. However, the molecular mechanisms by which Zn(II) affords protection have not been defined. We show that in Streptococcus pneumoniae extracellular Zn(II) inhibits the acquisition of the essential metal Mn(II) by competing for binding to the solute binding protein PsaA. We show that, although Mn(II) is the high-affinity substrate for PsaA, Zn(II) can still bind, albeit with a difference in affinity of nearly two orders of magnitude. Despite the difference in metal ion affinities, high-resolution structures of PsaA in complex with Mn(II) or Zn(II) showed almost no difference. However, Zn(II)-PsaA is significantly more thermally stable than Mn(II)-PsaA, suggesting that Zn(II) binding may be irreve