Cystatin inhibition of cathepsin B requires dislocation of the proteinase occluding loop. Demonstration by release of loop anchoring through mutationof His110
A. Pavlova et al., Cystatin inhibition of cathepsin B requires dislocation of the proteinase occluding loop. Demonstration by release of loop anchoring through mutationof His110, FEBS LETTER, 487(2), 2000, pp. 156-160
Cystatins A and C were both shown to inhibit cathepsin B by a two-step mech
anism, involving an initial weak interaction followed by a conformational c
hange. Disruption of the major salt bridge anchoring the occluding loop of
cathepsin B to the main body of the enzyme by mutation of His110 to Ala con
verted the binding to an apparent one-step reaction, The second step of cys
tatin binding to cathepsin B must therefore be due to the inhibitor having
to alter the conformation of the enzyme by displacing the occluding loop to
allow a tight complex to be formed. Cystatin A mas appreciably less effect
ive in displacing the loop than cystatin C, resulting in a considerably low
er overall inhibition rate constant. (C) 2000 Federation of European Bioche
mical Societies. Published by Elsevier Science B.V. All rights reserved.