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Crystal structure of human cystatin D, a cysteine peptidase inhibitor with restricted inhibition profile.

Alvarez Fernandez, Marcia LU ; Liang, Yu-He; Abrahamson, Magnus LU and Su, Xiao-Dong LU (2005) In Journal of Biological Chemistry 280(18). p.18221-18228
Abstract
Cystatins are natural inhibitors of papain-like (family C1) and legumain-related (family C13) cysteine peptidases. Cystatin D is a type 2 cystatin, a secreted inhibitor found in human saliva and tear fluid. Compared to its homologues, cystatin D presents an unusual inhibition profile with a preferential inhibition cathepsin S > cathepsin H > cathepsin L, and no inhibition of cathepsin B or pig legumain. To elucidate the structural reasons for this specificity, we have crystallized recombinant human Arg26-cystatin D and solved its structures at room temperature and at cryo conditions to 2.5 and 1.8 Å resolution, respectively. Human cystatin D presents the typical cystatin fold, with a five-stranded anti-parallel -sheet wrapped around... (More)
Cystatins are natural inhibitors of papain-like (family C1) and legumain-related (family C13) cysteine peptidases. Cystatin D is a type 2 cystatin, a secreted inhibitor found in human saliva and tear fluid. Compared to its homologues, cystatin D presents an unusual inhibition profile with a preferential inhibition cathepsin S > cathepsin H > cathepsin L, and no inhibition of cathepsin B or pig legumain. To elucidate the structural reasons for this specificity, we have crystallized recombinant human Arg26-cystatin D and solved its structures at room temperature and at cryo conditions to 2.5 and 1.8 Å resolution, respectively. Human cystatin D presents the typical cystatin fold, with a five-stranded anti-parallel -sheet wrapped around a five-turn -helix. The structures reveal differences in the peptidase-interacting regions when compared to other cystatins, providing plausible explanations to the restricted inhibitory specificity of cystatin D for some papain-like peptidases, and its lack of reactivity towards legumain-related enzymes.

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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Journal of Biological Chemistry
volume
280
issue
18
pages
18221 - 18228
publisher
ASBMB
external identifiers
  • wos:000228807200080
  • scopus:24044544232
ISSN
1083-351X
DOI
10.1074/jbc.M411914200
language
English
LU publication?
yes
id
66ed63f7-ed82-4f5e-9c5a-5a3dc39fafd7 (old id 133590)
date added to LUP
2007-07-04 14:16:49
date last changed
2017-11-19 03:28:42
@article{66ed63f7-ed82-4f5e-9c5a-5a3dc39fafd7,
  abstract     = {Cystatins are natural inhibitors of papain-like (family C1) and legumain-related (family C13) cysteine peptidases. Cystatin D is a type 2 cystatin, a secreted inhibitor found in human saliva and tear fluid. Compared to its homologues, cystatin D presents an unusual inhibition profile with a preferential inhibition cathepsin S &gt; cathepsin H &gt; cathepsin L, and no inhibition of cathepsin B or pig legumain. To elucidate the structural reasons for this specificity, we have crystallized recombinant human Arg26-cystatin D and solved its structures at room temperature and at cryo conditions to 2.5 and 1.8 Å resolution, respectively. Human cystatin D presents the typical cystatin fold, with a five-stranded anti-parallel -sheet wrapped around a five-turn -helix. The structures reveal differences in the peptidase-interacting regions when compared to other cystatins, providing plausible explanations to the restricted inhibitory specificity of cystatin D for some papain-like peptidases, and its lack of reactivity towards legumain-related enzymes.<br/><br>
This is the final, accepted and revised manuscript of this article. Use alternative location to go to the published article. Requires subscription.},
  author       = {Alvarez Fernandez, Marcia and Liang, Yu-He and Abrahamson, Magnus and Su, Xiao-Dong},
  issn         = {1083-351X},
  language     = {eng},
  number       = {18},
  pages        = {18221--18228},
  publisher    = {ASBMB},
  series       = {Journal of Biological Chemistry},
  title        = {Crystal structure of human cystatin D, a cysteine peptidase inhibitor with restricted inhibition profile.},
  url          = {http://dx.doi.org/10.1074/jbc.M411914200},
  volume       = {280},
  year         = {2005},
}