Cystatin inhibition of cathepsin B requires dislocation of the proteinase occluding loop. Demonstration by release of loop anchoring through mutation of His110
Author
Summary, in English
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.
Department/s
Publishing year
2000
Language
English
Pages
156-156
Publication/Series
FEBS Letters
Volume
487
Issue
2
Document type
Journal article
Publisher
Wiley-Blackwell
Topic
- Pharmacology and Toxicology
- Medicinal Chemistry
Status
Published
ISBN/ISSN/Other
- ISSN: 1873-3468