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Cystatin inhibition of cathepsin B requires dislocation of the proteinase occluding loop. Demonstration by release of loop anchoring through mutation of His110

Pavlova, A ; Mort, JS ; Abrahamson, Magnus LU and Bjork, I (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.
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author
; ; and
organization
publishing date
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}},
}