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

Summary, in English

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: Marcia Alvarez Fernandez; Yu-He Liang; Magnus Abrahamson; Xiao-Dong Su
• Department/s: Division of Clinical Chemistry and Pharmacology; Biochemistry and Structural Biology
• Publishing year: 2005
• Language: English
• Pages: 18221-18228
• Publication/Series: Journal of Biological Chemistry
• Volume: 280
• Issue: 18
• Full text: - 24 MB; Download statistics
• Links: http://dx.doi.org/10.1074/jbc.M411914200
• Document type: Journal article
• Publisher: American Society for Biochemistry and Molecular Biology
• Topic: Pharmacology and Toxicology; Medicinal Chemistry
• Status: Published
• ISBN/ISSN/Other: ISSN: 1083-351X