Transcriptional regulation, metal binding properties and structure of Pden1597, an unusual Zn transport protein from Paracoccus denitrificans [Protein Structure and Folding]
March 18th, 2015 by Handali, M., Neupane, D. P., Roychowdhury, H., Yukl, E. T.
ATP-binding cassette (ABC) transporters of the cluster 9 family are ubiquitous among bacteria and essential for acquiring Zn and Mn from the environment or, in the case of pathogens, from the host. These rely on a substrate binding protein (SBP) to coordinate the relevant metal with high affinity and specificity and subsequently release it to a membrane permease for translocation into the cytoplasm. Although a number of cluster 9 SBP structures have been determined, the structural attributes conferring Zn or Mn specificity remain ambiguous. Here we describe the gene expression profile, in vitro metal binding properties and crystal structure of a new cluster 9 SBP from Paracoccus denitrificans we have called AztC. Although all of our results strongly indicate Zn over Mn specificity, the Zn ion is coordinated by a conserved Asp residue only observed to date as a metal ligand in Mn-specific SBPs. The unusual sequence properties of this protein are shared among close homologues, including members from the human pathogens Klebsiella pneumonia and Enterobacter aerogenes, and would seem to suggest a sub-class of Zn-specific transporters among the cluster 9 family. In any case, the unusual coordination environment of AztC expands the already considerable range of those available to Zn-specific SBPs and highlights the presence of a His-rich loop as the most reliable indicator of Zn specificity.