title: The staphostatin family of cysteine protease inhibitors in the genus Staphylococcus as an example of parallel evolution of protease and inhibitor specificity.
abstract: Staphostatins constitute a family of staphylococcal cysteine protease inhibitors sharing a lipocalin-like fold and a unique mechanism of action. Each of these cytoplasmic proteins is co-expressed from one operon, together with a corresponding target extracellular cysteine protease (staphopain). To cast more light on staphostatin/staphopain interaction and the evolution of the encoding operons, we have cloned and characterized a staphopain (StpA2aur CH-91) and its inhibitor (StpinA2aur CH-91) from a novel staphylococcal thiol protease operon (stpAB2CH-91) identified in S. aureus strain CH-91. Furthermore, we have expressed a staphostatin from Staphylococcus warneri (StpinBwar) and characterized its target protease (StpBwar). Analysis of the reciprocal interactions among novel and previously described members of the staphostatin and staphopain families demonstrates that the co-transcribed protease is the primary target for each staphostatin. Nevertheless, the inhibitor derived from one species of Staphylococcus can inhibit the staphopain from another species, although the Ki values are generally higher and inhibition only occurs if both proteins belong to the same subgroup of either S. aureus staphopain A/staphostatin A (alpha group) or staphopain B/staphostatin B (beta group) orthologs. This indicates that both subgroups arose in a single event of ancestral allelic duplication, followed by parallel evolution of the protease/inhibitor pairs. The tight coevolution is likely the result of the known deleterious effects of uncontrolled staphopain action.
authors.affiliation: Department of Microbiology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, 30-387 Krakow, Poland. gdubin@mol.uj.edu.pl
authors.forename: Grzegorz
authors.initials: G
authors.lastname: Dubin
authors.forename: Benedykt
authors.initials: B
authors.lastname: Wladyka
authors.forename: Justyna
authors.initials: J
authors.lastname: Stec-Niemczyk
authors.forename: Dorota
authors.initials: D
authors.lastname: Chmiel
authors.forename: Michal
authors.initials: M
authors.lastname: Zdzalik
authors.forename: Adam
authors.initials: A
authors.lastname: Dubin
authors.forename: Jan
authors.initials: J
authors.lastname: Potempa
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000235:genetics / Q000302:isolation & purification / Q000494:pharmacology*; D005075:Biological Evolution; D002352:Carrier Proteins / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D002645:Chickens; D003001:Cloning, Molecular; D003546:Cysteine Endopeptidases / Q000737:chemistry / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification; D047908:Intracellular Signaling Peptides and Proteins; D009876:Operon / Q000187:drug effects; D016133:Polymerase Chain Reaction; D011480:Protease Inhibitors / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D011994:Recombinant Proteins; D012680:Sensitivity and Specificity; D013210:Staphylococcus / Q000201:enzymology / Q000235:genetics*; D013379:Substrate Specificity
chemical_list: D001426:Bacterial Proteins; D002352:Carrier Proteins; D047908:Intracellular Signaling Peptides and Proteins; D011480:Protease Inhibitors; D011994:Recombinant Proteins; C501296:staphostatin A, Staphylococcus aureus; C479136:staphostatin B protein, Staphylococcus aureus; D003546:Cysteine Endopeptidases; C501295:staphopain A protein, Staphylococcus aureus; C479137:staphopain B protein, Staphylococcus aureus