title: Structure of Haemophilus influenzae Fe(+3)-binding protein reveals convergent evolution within a superfamily.
abstract: The first crystal structure of the iron-transporter ferric ion-binding protein from Haemophilus influenzae (hFBP), at 1.6 A resolution, reveals the structural basis for iron uptake and transport required by several important bacterial pathogens. Paradoxically, although hFBP belongs to a protein superfamily which includes human transferrin, iron binding in hFBP and transferrin appears to have developed independently by convergent evolution. Structural comparison of hFBP with other prokaryotic periplasmic transport proteins and the eukaryotic transferrins suggests that these proteins are related by divergent evolution from an anion-binding common ancestor, not from an iron-binding ancestor. The iron binding site of hFBP incorporates a water and an exogenous phosphate ion as iron ligands and exhibits nearly ideal octahedral metal coordination. FBP is highly conserved, required for virulence, and is a nodal point for free iron uptake in several Gram-negative pathogenic bacteria, thus providing a potential target for broad-spectrum antibacterial drug design against human pathogens such as H. influenzae, Neisseria gonorrhoeae, and Neisseria meningitidis.
authors.affiliation: Department of Molecular Biology MB8, Scripps Research Institute, La Jolla, California 92037, USA.
authors.forename: C M
authors.initials: CM
authors.lastname: Bruns
authors.forename: A J
authors.initials: AJ
authors.lastname: Nowalk
authors.forename: A S
authors.initials: AS
authors.lastname: Arvai
authors.forename: M A
authors.initials: MA
authors.lastname: McTigue
authors.forename: K G
authors.initials: KG
authors.lastname: Vaughan
authors.forename: T A
authors.initials: TA
authors.lastname: Mietzner
authors.forename: D E
authors.initials: DE
authors.lastname: McRee
mesh_terms: D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000737:chemistry*; D001665:Binding Sites; D002352:Carrier Proteins / Q000737:chemistry*; D018360:Crystallography, X-Ray; D019143:Evolution, Molecular; D006193:Haemophilus influenzae / Q000737:chemistry*; D007501:Iron / Q000378:metabolism*; D033862:Iron-Binding Proteins; D008958:Models, Molecular; D008969:Molecular Sequence Data; D017386:Sequence Homology, Amino Acid; D033863:Transferrin-Binding Proteins
chemical_list: D001426:Bacterial Proteins; D002352:Carrier Proteins; D033862:Iron-Binding Proteins; D033863:Transferrin-Binding Proteins; D007501:Iron