Advanced

Human cystatin C: Role of the N-terminal segment in the inhibition of human cysteine proteinases and in its inactivation by leucocyte elastase

Abrahamson, Magnus LU ; Mason, Robert W; Hansson, Heléne; Buttle, David J; Grubb, Anders LU and Ohlsson, Kjell (1991) In Biochemical Journal 273(3). p.621-626
Abstract
Leucocyte elastase in catalytic amounts was observed to rapidly cleave the Val-10-Gly-11 bond of the human cysteine-proteinase inhibitor cystatin C at neutral pH. The resulting modified inhibitor had size and amino acid composition consistent with a cystatin C molecule devoid of the N-terminal Ser-1-Val-10 decapeptide. Leucocyte-elastase-modified cystatin C had more than 240-fold lower affinity than native cystatin C for papain. Removal of the N-terminal decapeptide of human cystatin C also decreased inhibition of human cathepsins B and L by three orders of magnitude, but decreased inhibition of cathepsin H by only 5-fold. A tripeptidyldiazomethane analogue of of the N-terminal portion of cystatin C was a good inhibitor of cathepsins B and... (More)
Leucocyte elastase in catalytic amounts was observed to rapidly cleave the Val-10-Gly-11 bond of the human cysteine-proteinase inhibitor cystatin C at neutral pH. The resulting modified inhibitor had size and amino acid composition consistent with a cystatin C molecule devoid of the N-terminal Ser-1-Val-10 decapeptide. Leucocyte-elastase-modified cystatin C had more than 240-fold lower affinity than native cystatin C for papain. Removal of the N-terminal decapeptide of human cystatin C also decreased inhibition of human cathepsins B and L by three orders of magnitude, but decreased inhibition of cathepsin H by only 5-fold. A tripeptidyldiazomethane analogue of of the N-terminal portion of cystatin C was a good inhibitor of cathepsins B and L but a poor inhibitor of cathepsin H. It therefore appears that amino acid side chains of the N-terminal segment of cystatin C bind in the substrate-binding pockets of cathepsins B and L but not in those of cathepsin H. It is argued that the N-terminal cystatin C interaction with cathepsin B is physiologically important and hence that leucocyte elastase could have a function as a regulator of extracellular cysteine-proteinase inhibitory activity at sites of inflammation. (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Biochemical Journal
volume
273
issue
3
pages
621 - 626
publisher
Portland Press Limited
external identifiers
  • scopus:0025964356
ISSN
0264-6021
language
English
LU publication?
yes
id
e74fd18a-636a-4d47-8e81-b3c4af3b179b (old id 1106096)
alternative location
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1149809
http://www.biochemj.org/bj/273/bj2730621.htm
date added to LUP
2008-08-01 09:49:30
date last changed
2017-08-27 05:25:04
@article{e74fd18a-636a-4d47-8e81-b3c4af3b179b,
  abstract     = {Leucocyte elastase in catalytic amounts was observed to rapidly cleave the Val-10-Gly-11 bond of the human cysteine-proteinase inhibitor cystatin C at neutral pH. The resulting modified inhibitor had size and amino acid composition consistent with a cystatin C molecule devoid of the N-terminal Ser-1-Val-10 decapeptide. Leucocyte-elastase-modified cystatin C had more than 240-fold lower affinity than native cystatin C for papain. Removal of the N-terminal decapeptide of human cystatin C also decreased inhibition of human cathepsins B and L by three orders of magnitude, but decreased inhibition of cathepsin H by only 5-fold. A tripeptidyldiazomethane analogue of of the N-terminal portion of cystatin C was a good inhibitor of cathepsins B and L but a poor inhibitor of cathepsin H. It therefore appears that amino acid side chains of the N-terminal segment of cystatin C bind in the substrate-binding pockets of cathepsins B and L but not in those of cathepsin H. It is argued that the N-terminal cystatin C interaction with cathepsin B is physiologically important and hence that leucocyte elastase could have a function as a regulator of extracellular cysteine-proteinase inhibitory activity at sites of inflammation.},
  author       = {Abrahamson, Magnus and Mason, Robert W and Hansson, Heléne and Buttle, David J and Grubb, Anders and Ohlsson, Kjell},
  issn         = {0264-6021},
  language     = {eng},
  number       = {3},
  pages        = {621--626},
  publisher    = {Portland Press Limited},
  series       = {Biochemical Journal},
  title        = {Human cystatin C: Role of the N-terminal segment in the inhibition of human cysteine proteinases and in its inactivation by leucocyte elastase},
  volume       = {273},
  year         = {1991},
}