Crystal structure of calcium bound domain VI of calpain at 1.9 Å resolution and its role in enzyme assembly, regulation, and inhibitor binding

Autor:	Mike Carson, Guang-da Lin, Masatoshi Maki, Lei Jin, Kevin K.W. Wang, Emiko Takano, Sthanam V.L. Narayana, Po-Wai Yuen, Lawrence J. DeLucas, Debasish Chattopadhyay, Masakazu Hatanaka
Rok vydání:	1997
Předmět:	chemistry.chemical_classification biology Stereochemistry Resolution (electron density) chemistry.chemical_element Calpain Crystal structure Calcium Biochemistry Crystallography Enzyme chemistry Structural Biology Domain (ring theory) Genetics biology.protein Molecule Binding domain
Zdroj:	Nature Structural Biology. 4:539-547
ISSN:	1072-8368
DOI:	10.1038/nsb0797-539
Popis:	The three dimensional structure of calcium-bound domain VI of porcine calpain has been determined to 1.9 A resolution. The crystal structure reveals five EF-hands, one more than previously suggested. There are two EF-hand pairs, one pair (EF1-EF2) displays an ‘open’ conformation and the other (EF3-EF4) a ‘closed’ conformation. Unusually, a calcium atom is found at the C-terminal end of the calcium binding loop of EF4. With two additional residues in the calcium binding loop, the fifth EF-hand (EF5) is in a ‘closed’ conformation. EF5 pairs up with the corresponding fifth EF-hand of a non-crystallographically related molecule. Considering the EFS's role in a homodimer formation of domain VI, we suggest a model for the assembly of heterodimeric calpain. The crystal structure of a Ca2+ bound domain VI–inhibitor (PD150606) complex has been refined to 2.1 A resolution. A possible mode for calpain inhibition is discussed.
Databáze:	OpenAIRE
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