title: Tissue kallikrein inhibitors in mammals.
abstract: We have discovered, purified and cloned a new kallikrein-binding protein (KBP or kallistatin) from humans and rodents. Kallistatins are members of the serine proteinase inhibitor (serpin) superfamily. They are acidic glycoproteins with molecular masses of 58-62 kDa and pI values of 4.6-5.2. Kallistatin forms a SDS-stable complex with tissue kallikrein and inhibits kallikrein's activities. Human kallistatin has a unique cleavage site with Phe-Phe-Ser at the P2-P1-P1' positions. The protein sequence of mature human kallistatin shares 44-46% identity with other serpins such as human alpha 1-antitrypsin, protein C inhibitor and rat kallikrein-binding protein. The kallistatin genes display the typical five exon-four intron serpin gene structure. The human kallistatin gene is localized on chromosome 14q31-32.1 and the RKBP gene is on chromosome 6. Kallistatin is evolutionarily diverse but functionally conserved in mammalian species. This overview summarizes the biochemistry, molecular biology and potential physiology and/or pathophysiology of this new tissue kallikrein inhibitor.
authors.affiliation: Department of Biochemistry and Molecular Biology, Medical University of South Carolina, Charleston, USA.
authors.forename: J
authors.initials: J
authors.lastname: Chao
authors.forename: K X
authors.initials: KX
authors.lastname: Chai
authors.forename: L
authors.initials: L
authors.lastname: Chao
mesh_terms: D000818:Animals; D006801:Humans; D007610:Kallikreins / Q000037:antagonists & inhibitors* / Q000187:drug effects* / Q000378:metabolism; D020840:Tissue Kallikreins
chemical_list: D007610:Kallikreins; D020840:Tissue Kallikreins