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:
https://lup.lub.lu.se/record/1106096
- author
- Abrahamson, Magnus
LU
; Mason, Robert W
; Hansson, Heléne
; Buttle, David J
; Grubb, Anders
LU
and Ohlsson, Kjell
- organization
- publishing date
- 1991
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Biochemical Journal
- volume
- 273
- issue
- 3
- pages
- 621 - 626
- publisher
- Portland Press
- 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
- 2016-04-01 16:19:04
- date last changed
- 2021-01-31 04:27:13
@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}},
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}},
url = {{http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1149809}},
volume = {{273}},
year = {{1991}},
}