1UCH

DEUBIQUITINATING ENZYME UCH-L3 (HUMAN) AT 1.8 ANGSTROM RESOLUTION

Summary for 1UCH

• Entry DOI: 10.2210/pdb1uch/pdb
• Descriptor: UBIQUITIN C-TERMINAL HYDROLASE UCH-L3 (2 entities in total)
• Functional Keywords: cysteine protease, deubiquitinating enzyme, ubiquitin, c-terminal hydrolase, ubiquitin conjugation
• Biological source: Homo sapiens (human)
• Cellular location: Cytoplasm: P15374
• Total number of polymer chains: 1
• Total formula weight: 26213.58

Authors

Johnston, S.C.,Larsen, C.N.,Cook, W.J.,Wilkinson, K.D.,Hill, C.P. (deposition date: 1997-10-06, release date: 1998-01-28, Last modification date: 2024-02-14)

Primary citation

Johnston, S.C.,Larsen, C.N.,Cook, W.J.,Wilkinson, K.D.,Hill, C.P.
Crystal structure of a deubiquitinating enzyme (human UCH-L3) at 1.8 A resolution.
EMBO J., 16:3787-3796, 1997

PubMed Abstract: Ubiquitin C-terminal hydrolases catalyze the removal of adducts from the C-terminus of ubiquitin. We have determined the crystal structure of the recombinant human Ubiquitin C-terminal Hydrolase (UCH-L3) by X-ray crystallography at 1.8 A resolution. The structure is comprised of a central antiparallel beta-sheet flanked on both sides by alpha-helices. The beta-sheet and one of the helices resemble the well-known papain-like cysteine proteases, with the greatest similarity to cathepsin B. This similarity includes the UCH-L3 active site catalytic triad of Cys95, His169 and Asp184, and the oxyanion hole residue Gln89. Papain and UCH-L3 differ, however, in strand and helix connectivity, which in the UCH-L3 structure includes a disordered 20 residue loop (residues 147-166) that is positioned over the active site and may function in the definition of substrate specificity. Based upon analogy with inhibitor complexes of the papain-like enzymes, we propose a model describing the binding of ubiquitin to UCH-L3. The UCH-L3 active site cleft appears to be masked in the unliganded structure by two different segments of the enzyme (residues 9-12 and 90-94), thus implying a conformational change upon substrate binding and suggesting a mechanism to limit non-specific hydrolysis.

PubMed: 9233788
DOI: 10.1093/emboj/16.13.3787

Experimental method

X-RAY DIFFRACTION (1.8 Å)