1ROA

Structure of human cystatin D

Summary for 1ROA

• Entry DOI: 10.2210/pdb1roa/pdb
• Related: 1RN7
• Descriptor: Cystatin D (2 entities in total)
• Functional Keywords: inhibitor of cysteine pepidases, cystatin d, protein binding
• Biological source: Homo sapiens (human)
• Cellular location: Secreted : P28325
• Total number of polymer chains: 1
• Total formula weight: 13927.62

Authors

Alvarez-Fernandez, M.,Liang, Y.H.,Abrahamson, M.,Su, X.D. (deposition date: 2003-12-01, release date: 2004-05-18, Last modification date: 2024-10-30)

Primary citation

Alvarez-Fernandez, M.,Liang, Y.H.,Abrahamson, M.,Su, X.D.
Crystal structure of human cystatin D, a cysteine peptidase inhibitor with restricted inhibition profile.
J.Biol.Chem., 280:18221-18228, 2005

PubMed 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 with 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 Arg(26)-cystatin D and solved its structures at room temperature and at cryo conditions to 2.5- and 1.8-A resolution, respectively. Human cystatin D presents the typical cystatin fold, with a five-stranded anti-parallel beta-sheet wrapped around a five-turn alpha-helix. The structures reveal differences in the peptidase-interacting regions when compared with other cystatins, providing plausible explanations for the restricted inhibitory specificity of cystatin D for some papain-like peptidases and its lack of reactivity toward legumain-related enzymes.

PubMed: 15728581
DOI: 10.1074/jbc.M411914200

Experimental method

X-RAY DIFFRACTION (1.8 Å)