A tick protein with a modified Kunitz fold inhibits human tryptase

Paesen, Guido C.; Siebold, Christian; Harlos, Karl; Peacey, Mick F.; Nuttall, Patricia A.; Suart, David I.. 2007 A tick protein with a modified Kunitz fold inhibits human tryptase. Journal of Molecular Biology, 368 (4). 1172-1186.

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TdPI, a tick salivary gland product related to Kunitz/BPTI proteins is a potent inhibitor of human β-tryptase. Kinetic assays suggest that three of the four catalytic sites of tryptase are blocked by TdPI, and that the inhibition of one of these involves a peptide flanking the Kunitz head. In the course of the inhibition, tryptase cleaves TdPI at several positions. Crystal structures of the TdPI head, on its own and in complex with trypsin, reveal features that are not found in classical Kunitz/BPTI proteins and suggest the mode of interaction with tryptase. The loop of TdPI connecting the β-sheet with the C-terminal α-helix is shortened, the disulphide-bridge pattern altered and N and C termini separated to produce a highly pointed molecule capable of penetrating the cramped active sites of tryptase. TdPI accumulates in the cytosolic granules of mast cells, presumably suppressing inflammation in the host animal's skin by tryptase inhibition.

Item Type: Publication - Article
Digital Object Identifier (DOI):
Programmes: CEH Programmes pre-2009 publications > Biodiversity
UKCEH and CEH Sections/Science Areas: Hails
ISSN: 0022-2836
Additional Keywords: Kunitz, tick, trypsin, tryptase, structure
NORA Subject Terms: Biology and Microbiology
Date made live: 27 Nov 2007 16:57 +0 (UTC)

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