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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 Lett 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
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
FEBS Lett
volume
487
issue
2
pages
156 - 156
publisher
Wiley-Blackwell
external identifiers
  • Scopus:0034731319
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
2008-06-17 14:00:35
date last changed
2016-11-17 15:32:48
@misc{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},
  language     = {eng},
  number       = {2},
  pages        = {156--156},
  publisher    = {ARRAY(0x8204fd0)},
  series       = {FEBS Lett},
  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},
  volume       = {487},
  year         = {2000},
}