The cystatins: Protein inhibitors of cysteine proteinases

Abstract

The iast decade has witnessed enormous progress of protein inhibitors of cysteine proteinases concerning their structures, functions and evolutionary relationships. Although they differ in their molecular properties and biological distribution, they are structurally related proteins. All three inhibitory families, the stetins, the cystatins and the kininogens, are members of the same superfamily. Recently determined crystal structures of chicken cystatin and human stefin B established a new mechanism of interaction between cysteine proteinases and their inhibitors which is fundamentally different from the standard mechanism for serine proteinases and their inhibitors.

Interaction of human cathepsin C with chicken cystatin

“…Cathepsin C is inhibited by stefins A and B [13][14][15] and chicken cystatin [13,16], three protein inhibitors of cysteine proteinases from the cystatin superfamily [17]. All inhibitors were shown to be of the competitive, reversible type, with stefin A being the weakest by 2-3 orders of magnitude [13][14][15][16].…”

A membrane‐associated cysteine protease inhibitor from murine hepatoma

“…and has been subdivided into three families: stcfins. cystutins, and kinincgcns (for rcvicw, see [4,5)). The stcfins are primarily intrnccllular cytosolic proteins.…”

Friends and relations of the cystatin superfamily—new members and their evolution

“…The cystatins are a family of cysteine protease inhibitors with homology to chicken cystatin (Barrett, 1981). Cystatins typically comprise = 1 15 amino acids, are largely acidic, contain four conserved cysteine residues known to form two disulfide bonds (Grubb et a]., 1984), may be glycosylated and/or phosphorylated, and contain a series of conserved residues, most notably the "QVVAG' sequence (reviewed in Rawlings & Barrett, 1990;Turk & Bode, 1991).…”

“…Protein, cDNA, and genomic sequences of several cystatins have since been reported (e.g., Tsai et al, 1996; reviewed in Rawlings & Barrett, 1990;Turk & Bode, 1991). Their structural genes comprise three exons of characteristic size (e.g., Huh et al, 1995) (Fig.…”

“…The cystatins are a family of cysteine protease inhibitors with homology to chicken cystatin (Barrett, 1981). Cystatins typically comprise = 1 15 amino acids, are largely acidic, contain four conserved cysteine residues known to form two disulfide bonds (Grubb et a]., 1984), may be glycosylated and/or phosphorylated, and contain a series of conserved residues, most notably the "QVVAG' sequence (reviewed in Rawlings & Barrett, 1990;Turk & Bode, 1991).Protein, cDNA, and genomic sequences of several cystatins have since been reported (e.g., Tsai et al, 1996; reviewed in Rawlings & Barrett, 1990;Turk & Bode, 1991). Their structural genes comprise three exons of characteristic size (e.g., Huh et al, 1995) (Fig.…”