tailieunhanh - Báo cáo khoa học: The crystal structure of human WD40 repeat-containing peptidylprolyl isomerase (PPWD1)

Cyclophilins comprise one of the three classes of peptidylprolyl isomerases found in all eukaryotic and prokaryotic organisms, as well as viruses. Many of the 17 annotated human cyclophilins contain the catalytic domain in tandem with other domains, and many of the specific functions of a par-ticular cyclophilin or its associated domains remain unknown. | ỊFEBS Journal The crystal structure of human WD40 repeat-containing peptidylprolyl isomerase PPWD1 Tara L. Davis1 2 John R. Walker1 Hui Ouyang1 Farrell MacKenzie1 Christine Butler-Cole1 Elena M. Newman1 Elan Z. Eisenmesser3 and Sirano Dhe-Paganon1 2 1 StructuralGenomics Consortium Banting Institute University of Toronto Canada 2 Department of Physiology University of Toronto Canada 3 Department of Biochemistry and Molecular Genetics University of Colorado Denver and Health Sciences Center Aurora CO USA Keywords crystal structure cyclophilin peptidyl-prolyl isomerase spliceosome WD40 Correspondence S. Dhe-Paganon StructuralGenomics Consortium Banting Institute University of Toronto 100 College Street Room 511 Toronto ON Canada M5G 1L5 Fax 1 416 946 0588 Tel 1 416 946 3876 E-mail Received 18 January 2008 revised 3 March 2008 accepted 6 March 2008 doi Cyclophilins comprise one of the three classes of peptidylprolyl isomerases found in all eukaryotic and prokaryotic organisms as well as viruses. Many of the 17 annotated human cyclophilins contain the catalytic domain in tandem with other domains and many of the specific functions of a particular cyclophilin or its associated domains remain unknown. The structure of the isomerase domain from a spliceosome-associated cyclophilin PPWD1 peptidylprolyl isomerase containing WD40 repeat has been solved to A. In the crystal the N-terminus of one isomerase domain is bound in the active site of a neighboring isomerase molecule in a manner analogous to substrate. NMR solution studies show that this sequence binds to the active site of the cyclophilin but cannot be turned over by the enzyme. A pseudo-substrate immediately N-terminal to the cyclophilin domain in PPWD1 could have wider implications for the function of this cyclophilin in the spliceosome where it is located in human cells. Cyclophilins Cyps are one of three subfamilies of the peptidylprolyl .