Crystal structure of human cystatin D, a cysteine peptidase inhibitor with restricted inhibition profile.
(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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Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/133590
- author
- Alvarez Fernandez, Marcia LU ; Liang, Yu-He ; Abrahamson, Magnus LU and Su, Xiao-Dong LU
- organization
- publishing date
- 2005
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Journal of Biological Chemistry
- volume
- 280
- issue
- 18
- pages
- 18221 - 18228
- publisher
- American Society for Biochemistry and Molecular Biology
- 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
- 2016-04-01 11:49:09
- date last changed
- 2022-01-26 18:41:20
@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 > 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.<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 = {{American Society for Biochemistry and Molecular Biology}}, series = {{Journal of Biological Chemistry}}, title = {{Crystal structure of human cystatin D, a cysteine peptidase inhibitor with restricted inhibition profile.}}, url = {{https://lup.lub.lu.se/search/files/2655689/624382.pdf}}, doi = {{10.1074/jbc.M411914200}}, volume = {{280}}, year = {{2005}}, }