Inhibitors of cysteine proteases [1,2,3], which are found in the tissues and
body fluids of animals, in the larva of the worm Onchocerca volvulus , as
well as in plants, can be grouped into three distinct but related families:
Type 1 cystatins (or stefins), molecules of about 100 amino acid residues
with neither disulfide bonds nor carbohydrate groups.
Type 2 cystatins, molecules of about 115 amino acid residues which contain
one or two disulfide loops near their C-terminus.
Kininogens, which are multifunctional plasma glycoproteins. They are the
precursor of the active peptide bradykinin and play a role in blood
coagulation by helping to position optimally prekallikrein and factor XI
next to factor XII. They are also inhibitors of cysteine proteases.
Structurally, kininogens are made of three contiguous type-2 cystatin
domains, followed by an additional domain (of variable length) which
contains the sequence of bradykinin. The first of the three cystatin
domains seems to have lost its inhibitory activity.
In all these inhibitors, there is a conserved region of five residues which
has been proposed to be important for the binding to the cysteine proteases.
Our pattern starts one residue before this conserved region.
This pattern is always twice in kininogens.
Members of the fetuin family (see <PDOC00966>) contain two copies of a
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