Allosteric control of βiI-tryptase by a redox active disulfide bond

Kristina M. Cook, H. Patrick McNeil, Philip J. Hogg*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

18 Citations (Scopus)


The S1A serine proteases function in many key biological processes such as development, immunity, and blood coagulation. S1A proteases contain a highly conserved disulfide bond (Cys191-Cys220 in chymotrypsin numbering) that links two β-loop structures that define the rim of the active site pocket. Mast cell βII-tryptase is a S1A protease that is associated with pathological inflammation. In this study, we have found that the conserved disulfide bond (Cys220-Cys248 in βII-tryptase) exists in oxidized and reduced states in the enzyme stored and secreted by mast cells. The disulfide bond has a standard redox potential of -301 mV and is stoichiometrically reduced by the inflammatory mediator, thioredoxin, with a rate constant of 350 M-1 s-1. The oxidized and reduced enzymes have different substrate specificity and catalytic efficiency for hydrolysis of both small and macromolecular substrates. These observations indicate that βII-tryptase activity is post-translationally regulated by an allosteric disulfide bond. It is likely that other S1A serine proteases are similarly regulated.

Original languageEnglish
Pages (from-to)34920-34929
Number of pages10
JournalJournal of Biological Chemistry
Issue number48
Publication statusPublished - 29 Nov 2013
Externally publishedYes


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