Cystatin inhibition of cathepsin B requires dislocation of the proteinase occluding loop. Demonstration By release of loop anchoring through mutation of his110.

Abstract:

:Cystatins A and C were both shown to inhibit cathepsin B by a two-step mechanism, involving an initial weak interaction followed by a conformational change. 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 converted the binding to an apparent one-step reaction. The second step of cystatin 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 was appreciably less effective in displacing the loop than cystatin C, resulting in a considerably lower overall inhibition rate constant.

journal_name

FEBS Lett

journal_title

FEBS letters

authors

Pavlova A,Krupa JC,Mort JS,Abrahamson M,Björk I

doi

10.1016/s0014-5793(00)02337-1

keywords:

subject

Has Abstract

pub_date

2000-12-29 00:00:00

pages

156-60

issue

2

eissn

0014-5793

issn

1873-3468

pii

S0014-5793(00)02337-1

journal_volume

487

pub_type

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