Crystal Structure of Human Cystatin D, a Cysteine Peptidase Inhibitor with Restricted Inhibition Profile
| Autor: | Yu-He Liang, Magnus Abrahamson, Marcia Alvarez-Fernandez, Xiao-Dong Su |
|---|---|
| Rok vydání: | 2005 |
| Předmět: |
Cathepsin H
Swine Cathepsin L Molecular Sequence Data Pharmacology and Toxicology Cysteine Proteinase Inhibitors Crystallography X-Ray urologic and male genital diseases Legumain Biochemistry Cathepsin B Cathepsin L1 Animals Humans Amino Acid Sequence Molecular Biology reproductive and urinary physiology Cathepsin S biology Cell Biology Cathepsins Cystatins Molecular biology Recombinant Proteins female genital diseases and pregnancy complications Cysteine Endopeptidases Cystatin A biology.protein Cystatin Medicinal Chemistry Crystallization |
| Zdroj: | Journal of Biological Chemistry; 280(18), pp 18221-18228 (2005) |
| ISSN: | 0021-9258 1083-351X |
| Popis: | 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. This is the final, accepted and revised manuscript of this article. Use alternative location to go to the published article. Requires subscription. |
| Databáze: | OpenAIRE |
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