title: Crystal structure of Pasteurella haemolytica ferric ion-binding protein A reveals a novel class of bacterial iron-binding proteins.
abstract: Pasteurellosis caused by the Gram-negative pathogen Pasteurella haemolytica is a serious disease leading to death in cattle. To scavenge growth-limiting iron from the host, the pathogen utilizes the periplasmic ferric ion-binding protein A (PhFbpA) as a component of an ATP-binding cassette transport pathway. We report the 1.2-A structure of the iron-free (apo) form of PhFbpA, which is a member of the transferrin structural superfamily. The protein structure adopts a closed conformation, allowing us to reliably assign putative iron-coordinating residues. Based on our analysis, PhFbpA utilizes a unique constellation of binding site residues and anions to octahedrally coordinate an iron atom. A surprising finding in the structure is the presence of two formate anions on opposite sides of the iron-binding pocket. The formate ions tether the N- and C-terminal domains of the protein and stabilize the closed structure, also providing clues as to probable candidates for synergistic anions in the iron-loaded state. PhFbpA represents a new class of bacterial iron-binding proteins.
authors.affiliation: Department of Microbiology and Infectious Diseases, University of Calgary, Calgary, Alberta T2N 4N1, Canada.
authors.forename: Stephen R
authors.initials: SR
authors.lastname: Shouldice
authors.forename: Douglas R
authors.initials: DR
authors.lastname: Dougan
authors.forename: Pamela A
authors.initials: PA
authors.lastname: Williams
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Skene
authors.forename: Gyorgy
authors.initials: G
authors.lastname: Snell
authors.forename: Daniel
authors.initials: D
authors.lastname: Scheibe
authors.forename: Shane
authors.initials: S
authors.lastname: Kirby
authors.forename: David J
authors.initials: DJ
authors.lastname: Hosfield
authors.forename: Duncan E
authors.initials: DE
authors.lastname: McRee
authors.forename: Anthony B
authors.initials: AB
authors.lastname: Schryvers
authors.forename: Leslie W
authors.initials: LW
authors.lastname: Tari
mesh_terms: D001425:Bacterial Outer Membrane Proteins; D001426:Bacterial Proteins / Q000737:chemistry* / Q000145:classification; D001665:Binding Sites; D018360:Crystallography, X-Ray; D004926:Escherichia coli / Q000378:metabolism; D007477:Ions; D007501:Iron / Q000378:metabolism*; D033862:Iron-Binding Proteins; D016978:Mannheimia haemolytica / Q000378:metabolism*; D008958:Models, Molecular; D033902:Periplasmic Binding Proteins; D011485:Protein Binding; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D014168:Transferrin / Q000737:chemistry / Q000378:metabolism
chemical_list: D001425:Bacterial Outer Membrane Proteins; D001426:Bacterial Proteins; D007477:Ions; D033862:Iron-Binding Proteins; D033902:Periplasmic Binding Proteins; D014168:Transferrin; D007501:Iron