%0 Journal Article
%T Delineation of the Pasteurellaceae-specific GbpA-family of glutathione-binding proteins
%A Bjorn Vergauwen
%A Ruben Van der Meeren
%A Ann Dansercoer
%A Savvas N Savvides
%J BMC Biochemistry
%D 2011
%I BioMed Central
%R 10.1186/1471-2091-12-59
%X Lipoprotein and non-lipoprotein GbpA homologs were expressed in soluble form and substrate specificity was evaluated via a number of ligand binding assays. A physiologically insignificant affinity for hemin was observed for all five GbpA homologous test proteins. Three out of five test proteins were found to bind glutathione and some of its physiologically relevant derivatives with low- or submicromolar affinity. None of the tested SBP family 5 allocrites interacted with the remaining two GbpA test proteins. Structure-based sequence alignments and phylogenetic analysis show that the two binding-inert GbpA homologs clearly form a separate phylogenetic cluster. To elucidate a structure-function rationale for this phylogenetic differentiation, we determined the crystal structure of one of the GbpA family outliers from H. parasuis. Comparisons thereof with the previously determined structure of GbpA in complex with oxidized glutathione reveals the structural basis for the lack of allocrite binding capacity, thereby explaining the outlier behavior.Taken together, our studies provide for the first time a collective functional look on a novel, Pasteurellaceae-specific, SBP subfamily of glutathione binding proteins, which we now term GbpA proteins. Our studies strongly implicate GbpA family SBPs in the priming step of ABC-transporter-mediated translocation of useful forms of glutathione across the inner membrane, and rule out a general role for GbpA proteins in heme acquisition.ATP-binding cassette (ABC)-transporters exist in all three kingdoms of life and transport a large variety of substrates across biological membranes. In addition to their well-documented role in solute transport, a diversity of sensory functions have been assigned that implicate ABC-transporters in the maintenance of cell integrity, responses to environmental stresses, cell-to-cell communication and cell differentiation and in pathogenicity. Based on the direction of transport, ABC transporters can be
%K glutathione
%K GbpA
%K HbpA
%K DppA
%K solute-binding protein
%K SBP
%K ABC transporter
%U http://www.biomedcentral.com/1471-2091/12/59