title: Crystal structure of FhuD at 1.6 Å resolution: a ferrichrome-binding protein from the animal and human pathogen Staphylococcus pseudintermedius.
abstract: Staphylococcus pseudintermedius is a leading cause of disease in dogs, and zoonosis causes human infections. Methicillin-resistant S. pseudintermedius strains are emerging, resembling the global health threat of S. aureus. Therefore, it is increasingly important to characterize potential targets for intervention against S. pseudintermedius. Here, FhuD, an S. pseudintermedius surface lipoprotein implicated in iron uptake, was characterized. It was found that FhuD bound ferrichrome in an iron-dependent manner, which increased the thermostability of FhuD by >15 °C. The crystal structure of ferrichrome-free FhuD was determined via molecular replacement at 1.6 Å resolution. FhuD exhibits the class III solute-binding protein (SBP) fold, with a ligand-binding cavity between the N- and C-terminal lobes, which is here occupied by a PEG molecule. The two lobes of FhuD were oriented in a closed conformation. These results provide the first detailed structural characterization of FhuD, a potential therapeutic target of S. pseudintermedius.
authors.affiliation: XBrane Biopharma, Stureplan 15, 111 45 Stockholm, Sweden.
authors.forename: Francesca
authors.initials: F
authors.lastname: Abate
authors.affiliation: Research Centre, GSK Vaccines Srl, Via Fiorentina 1, 53100 Siena, Italy.
authors.forename: Roberta
authors.initials: R
authors.lastname: Cozzi
authors.affiliation: Research Centre, GSK Vaccines Srl, Via Fiorentina 1, 53100 Siena, Italy.
authors.forename: Martina
authors.initials: M
authors.lastname: Maritan
authors.affiliation: Research Centre, GSK Vaccines Srl, Via Fiorentina 1, 53100 Siena, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Lo Surdo
authors.affiliation: Research Centre, GSK Vaccines Srl, Via Fiorentina 1, 53100 Siena, Italy.
authors.forename: Domenico
authors.initials: D
authors.lastname: Maione
authors.affiliation: Research Centre, GSK Vaccines Srl, Via Fiorentina 1, 53100 Siena, Italy.
authors.forename: Enrico
authors.initials: E
authors.lastname: Malito
authors.affiliation: Research Centre, GSK Vaccines Srl, Via Fiorentina 1, 53100 Siena, Italy.
authors.forename: Matthew James
authors.initials: MJ
authors.lastname: Bottomley
mesh_terms: D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000737:chemistry*; D002352:Carrier Proteins / Q000737:chemistry*; D003460:Crystallization; D018360:Crystallography, X-Ray; D005291:Ferrichrome / Q000737:chemistry; D026901:Membrane Transport Proteins / Q000737:chemistry*; D008958:Models, Molecular; D011485:Protein Binding; D055550:Protein Stability; D017262:Siderophores / Q000737:chemistry; D013210:Staphylococcus; D040681:Structural Homology, Protein
chemical_list: D001426:Bacterial Proteins; D002352:Carrier Proteins; D026901:Membrane Transport Proteins; D017262:Siderophores; D005291:Ferrichrome
keywords: class III solute-binding protein; iron; metal transport; siderophore; staphylococcal disease