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Two-step mechanism of inhibition of cathepsin B by cystatin C, due to the inhibitor displacing the occluding loop of the enzyme

Nycander, M; Estrada, S; Mort, J; Abrahamson, Magnus LU and Bjork, I (1998) In FEBS Letters 422(1). p.61-64
Abstract
Stopped-flow kinetics showed that the inhibition of the lysosomal cysteine proteinase, cathepsin B, by its endogenous inhibitor, cystatin C, occurs by a two-step mechanism, in which an initial, weak interaction is followed by a conformational change. The initial interaction most likely involves binding of the N-terminal region of the inhibitor to the proteinase. Considerable evidence indicates that the subsequent conformational change is due to the inhibitor displacing the occluding loop of the proteinase that partially obscures the active site. The presence of this loop, which allows the enzyme to function as an exopeptidase, thus complicates the inhibition mechanism, rendering cathepsin B much less susceptible than other cysteine... (More)
Stopped-flow kinetics showed that the inhibition of the lysosomal cysteine proteinase, cathepsin B, by its endogenous inhibitor, cystatin C, occurs by a two-step mechanism, in which an initial, weak interaction is followed by a conformational change. The initial interaction most likely involves binding of the N-terminal region of the inhibitor to the proteinase. Considerable evidence indicates that the subsequent conformational change is due to the inhibitor displacing the occluding loop of the proteinase that partially obscures the active site. The presence of this loop, which allows the enzyme to function as an exopeptidase, thus complicates the inhibition mechanism, rendering cathepsin B much less susceptible than other cysteine proteinases to inhibition by cystatins. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Cysteine proteinase, Cysteine proteinase inhibitor, Cathepsin, Cystatin, Kinetics
in
FEBS Letters
volume
422
issue
1
pages
61 - 64
publisher
Wiley-Blackwell
external identifiers
  • scopus:0032559423
ISSN
1873-3468
DOI
10.1016/S0014-5793(97)01604-9
language
English
LU publication?
yes
id
d5c1ff8e-0690-4d5e-85b5-097b38cc0bdd (old id 1113877)
date added to LUP
2008-07-16 12:57:57
date last changed
2017-02-26 04:14:05
@article{d5c1ff8e-0690-4d5e-85b5-097b38cc0bdd,
  abstract     = {Stopped-flow kinetics showed that the inhibition of the lysosomal cysteine proteinase, cathepsin B, by its endogenous inhibitor, cystatin C, occurs by a two-step mechanism, in which an initial, weak interaction is followed by a conformational change. The initial interaction most likely involves binding of the N-terminal region of the inhibitor to the proteinase. Considerable evidence indicates that the subsequent conformational change is due to the inhibitor displacing the occluding loop of the proteinase that partially obscures the active site. The presence of this loop, which allows the enzyme to function as an exopeptidase, thus complicates the inhibition mechanism, rendering cathepsin B much less susceptible than other cysteine proteinases to inhibition by cystatins.},
  author       = {Nycander, M and Estrada, S and Mort, J and Abrahamson, Magnus and Bjork, I},
  issn         = {1873-3468},
  keyword      = {Cysteine proteinase,Cysteine proteinase inhibitor,Cathepsin,Cystatin,Kinetics},
  language     = {eng},
  number       = {1},
  pages        = {61--64},
  publisher    = {Wiley-Blackwell},
  series       = {FEBS Letters},
  title        = {Two-step mechanism of inhibition of cathepsin B by cystatin C, due to the inhibitor displacing the occluding loop of the enzyme},
  url          = {http://dx.doi.org/10.1016/S0014-5793(97)01604-9},
  volume       = {422},
  year         = {1998},
}