title: Staphylokinase has distinct modes of interaction with antimicrobial peptides, modulating its plasminogen-activation properties.
abstract: Staphylokinase (Sak) is a plasminogen activator protein that is secreted by many Staphylococcus aureus strains. Sak also offers protection by binding and inhibiting specific antimicrobial peptides (AMPs). Here, we evaluate Sak as a more general interaction partner for AMPs. Studies with melittin, mCRAMP, tritrpticin and bovine lactoferricin indicate that the truncation of the first ten residues of Sak (SakΔN10), which occurs in vivo and uncovers important residues in a bulge region, improves its affinity for AMPs. Melittin and mCRAMP have a lower affinity for SakΔN10, and in docking studies, they bind to the N-terminal segment and bulge region of SakΔN10. By comparison, lactoferricin and tritrpticin form moderately high affinity 1:1 complexes with SakΔN10 and their cationic residues form several electrostatic interactions with the protein's α-helix. Overall, our work identifies two distinct AMP binding surfaces on SakΔN10 whose occupation would lead to either inhibition or promotion of its plasminogen activating properties.
authors.affiliation: Biochemistry Research Group, Department of Biological Sciences, University of Calgary, Calgary, Alberta, Canada.
authors.forename: Leonard T
authors.initials: LT
authors.lastname: Nguyen
authors.affiliation: Biochemistry Research Group, Department of Biological Sciences, University of Calgary, Calgary, Alberta, Canada.
authors.forename: Hans J
authors.initials: HJ
authors.lastname: Vogel
mesh_terms: D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000378:metabolism*; D001665:Binding Sites; D054804:Cathelicidins / Q000378:metabolism; D002417:Cattle; D007781:Lactoferrin / Q000378:metabolism; D008555:Melitten / Q000378:metabolism; D008666:Metalloendopeptidases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008958:Models, Molecular; D062105:Molecular Docking Simulation; D009842:Oligopeptides / Q000378:metabolism; D010958:Plasminogen / Q000378:metabolism*; D017433:Protein Structure, Secondary; D013211:Staphylococcus aureus / Q000737:chemistry / Q000201:enzymology* / Q000235:genetics; D013379:Substrate Specificity
chemical_list: D023181:Antimicrobial Cationic Peptides; D054804:Cathelicidins; D009842:Oligopeptides; C402895:tritrpticin; C082171:lactoferricin B; D008555:Melitten; D010958:Plasminogen; D007781:Lactoferrin; D008666:Metalloendopeptidases; C022653:auR protein, Staphylococcus aureus