Crystal structure of the de-ubiquitinating enzyme UCH37 (human UCH-L5) catalytic domain

• DOI: 10.1016/j.bbrc.2009.10.062
• Publication Date: 2009-10-16T08:19:32Z
• Authors: Kazuya Nishio; Sang-Woo Kim; Kentaro Kawai; Tsunehiro Mizushima; Takashi Yamane; Jun Hamazaki; Shigeo Murata; Keiji Tanaka; Yukio Morimoto
• Keywords: 0303 health sciences; 03 medical and health sciences; Ubiquitin; Catalytic Domain; Molecular Sequence Data; Humans; Amino Acid Sequence; Carboxypeptidases; Crystallography, X-Ray; Ubiquitin Thiolesterase; Protein Structure, Secondary

Ubiquitin C-terminal hydrolases (UCHs) are one of five sub-families of de-ubiquitinating enzymes (DUBs) that hydrolyze the C-terminal peptide bond of ubiquitin. UCH37 (also called UCH-L5) is the only UCH family protease that interacts with the 19S proteasome regulatory complex and disassembles Lys48-linked poly-ubiquitin from the distal end of the chain. The structures of three UCHs, UCH-L1, UCH-L3, and YUH1, have been determined by X-ray crystallography. However, little is known about their physiological substrates. These enzymes do not hydrolyze large adducts of ubiquitin such as proteins. To identify and characterize the hydrolytic specificities of their substrates, the crystal structure of the UCH37 catalytic domain (UCH-domain) was determined and compared with that of the other UCHs. The overall folding patterns are similar in these UCHs. However, helix-3 is collapsed in UCH37 and the pattern of electrostatic potential on the surface of the putative substrate-binding site (P'-site) is different. Helix-3 comprises an edge of the P'-site. As a result, the P'-site is wider than that in other UCHs. These differences indicate that UCH37 can interact with larger adducts such as ubiquitin.