Cystatin inhibition of cathepsin B requires dislocation of the proteinase occluding loop. Demonstration by release of loop anchoring through mutation of His110
(2000) In FEBS Letters 487(2). p.156-156- 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.
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/1118354
- author
- Pavlova, A ; Mort, JS ; Abrahamson, Magnus LU and Bjork, I
- organization
- publishing date
- 2000
- type
- Contribution to journal
- publication status
- published
- subject
- in
- FEBS Letters
- volume
- 487
- issue
- 2
- pages
- 156 - 156
- publisher
- Wiley-Blackwell
- external identifiers
-
- scopus:0034731319
- ISSN
- 1873-3468
- DOI
- 10.1016/S0014-5793(00)02337-1
- language
- English
- LU publication?
- yes
- id
- fc2699d1-e86e-4a09-88e9-ba8f230f34a7 (old id 1118354)
- date added to LUP
- 2016-04-04 10:29:33
- date last changed
- 2022-04-23 23:09:43
@article{fc2699d1-e86e-4a09-88e9-ba8f230f34a7, 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.}}, author = {{Pavlova, A and Mort, JS and Abrahamson, Magnus and Bjork, I}}, issn = {{1873-3468}}, language = {{eng}}, number = {{2}}, pages = {{156--156}}, publisher = {{Wiley-Blackwell}}, series = {{FEBS Letters}}, title = {{Cystatin inhibition of cathepsin B requires dislocation of the proteinase occluding loop. Demonstration by release of loop anchoring through mutation of His110}}, url = {{http://dx.doi.org/10.1016/S0014-5793(00)02337-1}}, doi = {{10.1016/S0014-5793(00)02337-1}}, volume = {{487}}, year = {{2000}}, }