4OXR

Structure of Staphylococcus pseudintermedius metal-binding protein SitA in complex with Manganese

Summary for 4OXR

• Entry DOI: 10.2210/pdb4oxr/pdb
• Related: 4OXQ
• Descriptor: Manganese ABC transporter, periplasmic-binding protein SitA, MANGANESE (II) ION (3 entities in total)
• Functional Keywords: manganese binding protein, sbp, abc transporter, metal binding protein
• Biological source: Staphylococcus pseudintermedius
• Total number of polymer chains: 2
• Total formula weight: 64484.06

Authors

Abate, F.,Malito, E.,Bottomley, M. (deposition date: 2014-02-06, release date: 2014-10-29, Last modification date: 2023-09-27)

Primary citation

Abate, F.,Malito, E.,Cozzi, R.,Lo Surdo, P.,Maione, D.,Bottomley, M.J.
Apo, Zn2+-bound and Mn2+-bound structures reveal ligand-binding properties of SitA from the pathogen Staphylococcus pseudintermedius.
Biosci.Rep., 34:e00154-e00154, 2014

PubMed Abstract: The Gram-positive bacterium Staphylococcus pseudintermedius is a leading cause of canine bacterial pyoderma, resulting in worldwide morbidity in dogs. S. pseudintermedius also causes life-threatening human infections. Furthermore, methicillin-resistant S. pseudintermedius is emerging, resembling the human health threat of methicillin-resistant Staphylococcus aureus. Therefore it is increasingly important to characterize targets for intervention strategies to counteract S. pseudintermedius infections. Here we used biophysical methods, mutagenesis, and X-ray crystallography, to define the ligand-binding properties and structure of SitA, an S. pseudintermedius surface lipoprotein. SitA was strongly and specifically stabilized by Mn2+ and Zn2+ ions. Crystal structures of SitA complexed with Mn2+ and Zn2+ revealed a canonical class III solute-binding protein with the metal cation bound in a cavity between N- and C-terminal lobes. Unexpectedly, one crystal contained both apo- and holo-forms of SitA, revealing a large side-chain reorientation of His64, and associated structural differences accompanying ligand binding. Such conformational changes may regulate fruitful engagement of the cognate ABC (ATP-binding cassette) transporter system (SitBC) required for metal uptake. These results provide the first detailed characterization and mechanistic insights for a potential therapeutic target of the major canine pathogen S. pseudintermedius, and also shed light on homologous structures in related staphylococcal pathogens afflicting humans.

PubMed: 25311310
DOI: 10.1042/BSR20140088

Experimental method

X-RAY DIFFRACTION (2 Å)