title: Functional differences between Streptococcus pyogenes cluster 1 and cluster 2b streptokinases are determined by their β-domains.
abstract: Cluster 1 streptokinases (SK1) from Streptococcus pyogenes (GAS) show substantially higher human plasminogen (hPg) activation activities and tighter hPg binding affinities than cluster 2b streptokinases (SK2b) in solution. The extent to which the different domains of SK are responsible for these differences is unknown. We exchanged each of the three known SK domains (α, β, and γ) between SK1 and SK2b and assessed the function of the resulting variants. Our results show that primary structural differences in the β-domains dictate these functional differences. This first report on the primary structure-functional relationship between naturally occurring SK1 and SK2b sheds new light on the mechanism of hPg activation by SK, a critical virulence determinant in this species of human pathogenic bacteria.
authors.affiliation: W.M. Keck Center for Transgene Research and Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, IN 46556, USA.
authors.forename: Yueling
authors.initials: Y
authors.lastname: Zhang
authors.forename: Zhong
authors.initials: Z
authors.lastname: Liang
authors.forename: Kristofor
authors.initials: K
authors.lastname: Glinton
authors.forename: Victoria A
authors.initials: VA
authors.lastname: Ploplis
authors.forename: Francis J
authors.initials: FJ
authors.lastname: Castellino
mesh_terms: D000595:Amino Acid Sequence; D017124:Conserved Sequence; D004789:Enzyme Activation; D006801:Humans; D008969:Molecular Sequence Data; D016296:Mutagenesis; D009154:Mutation; D010958:Plasminogen / Q000378:metabolism; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D013297:Streptococcus pyogenes / Q000201:enzymology*; D013300:Streptokinase / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D013329:Structure-Activity Relationship; D013379:Substrate Specificity
chemical_list: D010958:Plasminogen; D013300:Streptokinase