Đang chuẩn bị nút TẢI XUỐNG, xin hãy chờ
Tải xuống
Ubiquitin carboxy-terminal hydrolase L5 (UCHL5) is a proteasome-associ-ated deubiquitinating enzyme, which, along with RPN11 and USP14, is known to carry out deubiquitination on proteasome. As a member of the ubiquitin carboxy-terminal hydrolase (UCH) family, UCHL5 is unusual because, unlike UCHL1 and UCHL3, it can process polyubiquitin chain. | IFEBS Journal Crystal structure of the catalytic domain of UCHL5 a proteasome-associated human deubiquitinating enzyme reveals an unproductive form of the enzyme Tushar K. Maiti Michelle Permaul David A. Boudreaux Christina Mahanic Sarah Mauney and Chittaranjan Das Department of Chemistry Purdue University West Lafayette IN USA Keywords deubiquitination proteasome-associated deubiquitinases ubiquitin hydrolase UCHL5 unproductive active site Correspondence C. Das Department of Chemistry 560 Oval Drive West Lafayette IN 47907 USA Fax 1 765 494 0239 Tel 1 756 494 5478 E-mail cdas@purdue.edu These authors contributed equally to this work Received 6 July 2011 revised 1 October 2011 accepted 4 October 2011 doi 10.1111 j.1742-4658.2011.08393.x Ubiquitin carboxy-terminal hydrolase L5 UCHL5 is a proteasome-associ-ated deubiquitinating enzyme which along with RPN11 and USP14 is known to carry out deubiquitination on proteasome. As a member of the ubiquitin carboxy-terminal hydrolase UCH family UCHL5 is unusual because unlike UCHL1 and UCHL3 it can process polyubiquitin chain. However it does so only when it is bound to the proteasome in its free form it is capable of releasing only relatively small leaving groups from the C-terminus of ubiquitin. Such a behavior might suggest at least two catalytically distinct forms of the enzyme an apo form incapable of chain processing activity and a proteasome-induced activated form capable of cleaving polyubiquitin chain. Through the crystal structure analysis of two truncated constructs representing the catalytic domain UCH domain of this enzyme we were able to visualize a state of this enzyme that we interpret as its inactive form because the catalytic cysteine appears to be in an unproductive orientation. While this work was in progress the structure of a different construct representing the UCH domain was reported however in that work the structure reported was that of an inactive mutant catalytic Cys to Ala Nishio K et al. 2009 .
