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Research article - Peer-reviewed, 2019

Extended Cleavage Specificities of Rabbit and Guinea Pig Mast Cell Chymases: Two Highly Specific Leu-Ases

Yuan Zhongwei; Akula, Srinivas; Fu, Zhirong; de Garavilla, Lawrence; Kervinen, Jukka; Thorpe, Michael; Hellman, Lars


Serine proteases constitute the major protein content of mast cell (MC) secretory granules. These proteases can generally be subdivided into chymases and tryptases based on their primary cleavage specificity. Here, we presented the extended cleavage specificities of a rabbit beta-chymase and a guinea pig alpha-chymase. Analyses by phage display screening and a panel of recombinant substrates showed a marked similarity in catalytic activity between the enzymes, both being strict Leu-ases (cleaving on the carboxyl side of Leu). Amino acid sequence alignment of a panel of mammalian chymotryptic MC proteases and 3D structural modeling identified an unusual residue in the rabbit enzyme at position 216 (Thr instead of more common Gly), which is most likely critical for the Leu-ase specificity. Almost all mammals studied, except rabbit and guinea pig, express classical chymotryptic enzymes with similarly extended specificities, indicating an important role of chymase in MC biology. The rabbit and guinea pig are the only two mammalian species currently known to lack a classical MC chymase. Key questions are now how this major difference affects their MC function, and if genes of other loci can rescue the loss of a chymotryptic activity in MCs of these two species.


mast cells; chymase; tryptase; cleavage specificity; Leu-ase; phage display

Published in

International Journal of Molecular Sciences
2019, volume: 20, number: 24, article number: 6340
Publisher: MDPI

Authors' information

Zhongwei, Yuan
Uppsala University
Uppsala University
Fu, Zhirong
Uppsala University
de Garavilla, Lawrence
GDL Pharmaceut Consulting and Contracting
Kervinen, Jukka
Tosoh Biosci LLC
Thorpe, Michael
Uppsala University
Hellman, Lars
Uppsala University

UKÄ Subject classification

Biochemistry and Molecular Biology
Cell Biology

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