title: α1-Antichymotrypsin inactivates staphylococcal cysteine protease in cross-class inhibition.
abstract: Staphylococcal cysteine proteases are implicated as virulence factors in human and avian infections. Human strains of Staphylococcus aureus secrete two cysteine proteases (staphopains A and B), whereas avian strains express staphopain C (ScpA2), which is distinct from both human homologues. Here, we describe probable reasons why the horizontal transfer of a plasmid encoding staphopain C between avian and human strains has never been observed. The human plasma serine protease inhibitor α(1)-antichymotrypsin (ACHT) inhibits ScpA2. Together with the lack of ScpA2 inhibition by chicken plasma, these data may explain the exclusively avian occurrence of ScpA2. We also clarify the mechanistic details of this unusual cross-class inhibition. Analysis of mutated ACHT variants revealed that the cleavage of the Leu383-Ser384 peptide bond results in ScpA2 inhibition, whereas hydrolysis of the preceding peptide bond leads to ACHT inactivation. This evidence is consistent with the suicide-substrate-like mechanism of inhibition.
authors.affiliation: Department of Analytical Biochemistry, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Gronostajowa 7, 30-387 Krakow, Poland. wladykab@interia.pl
authors.forename: Benedykt
authors.initials: B
authors.lastname: Wladyka
authors.forename: Agata J
authors.initials: AJ
authors.lastname: Kozik
authors.forename: Michal
authors.initials: M
authors.lastname: Bukowski
authors.forename: Anna
authors.initials: A
authors.lastname: Rojowska
authors.forename: Tomasz
authors.initials: T
authors.lastname: Kantyka
authors.forename: Grzegorz
authors.initials: G
authors.lastname: Dubin
authors.forename: Adam
authors.initials: A
authors.lastname: Dubin
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D030161:Avian Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D002645:Chickens; D057056:Cysteine Proteases / Q000378:metabolism*; D015853:Cysteine Proteinase Inhibitors / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D004926:Escherichia coli; D006801:Humans; D006868:Hydrolysis; D007700:Kinetics; D050296:Microbial Viability / Q000187:drug effects; D016297:Mutagenesis, Site-Directed; D011485:Protein Binding; D011994:Recombinant Proteins / Q000096:biosynthesis; D013045:Species Specificity; D013211:Staphylococcus aureus / Q000201:enzymology*; D037521:Virulence Factors / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000514:alpha 1-Antichymotrypsin / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*
chemical_list: D030161:Avian Proteins; D015853:Cysteine Proteinase Inhibitors; D011994:Recombinant Proteins; D037521:Virulence Factors; D000514:alpha 1-Antichymotrypsin; D057056:Cysteine Proteases