1XD3

Crystal structure of UCHL3-UbVME complex

Summary for 1XD3

• Entry DOI: 10.2210/pdb1xd3/pdb
• Related: 1CMX 1UBQ 1UCH
• Descriptor: Ubiquitin Carboxyl-terminal esterase L3, UBC protein, MAGNESIUM ION, ... (5 entities in total)
• Functional Keywords: enzyme-ligand complex, active site crossover loop, hydrolase
• Biological source: Homo sapiens (human); More
• Cellular location: Cytoplasm: P15374
• Total number of polymer chains: 4
• Total formula weight: 69944.05

Authors

Misaghi, S.,Galardy, P.J.,Meester, W.J.N.,Ovaa, H.,Ploegh, H.L.,Gaudet, R. (deposition date: 2004-09-03, release date: 2004-11-23, Last modification date: 2023-11-15)

Primary citation

Misaghi, S.,Galardy, P.J.,Meester, W.J.N.,Ovaa, H.,Ploegh, H.L.,Gaudet, R.
Structure of the Ubiquitin Hydrolase UCH-L3 Complexed with a Suicide Substrate
J.Biol.Chem., 280:1512-1520, 2005

PubMed Abstract: Ubiquitin C-terminal hydrolases (UCHs) comprise a family of small ubiquitin-specific proteases of uncertain function. Although no cellular substrates have been identified for UCHs, their highly tissue-specific expression patterns and the association of UCH-L1 mutations with human disease strongly suggest a critical role. The structure of the yeast UCH Yuh1-ubiquitin aldehyde complex identified an active site crossover loop predicted to limit the size of suitable substrates. We report the 1.45 A resolution crystal structure of human UCH-L3 in complex with the inhibitor ubiquitin vinylmethylester, an inhibitor that forms a covalent adduct with the active site cysteine of ubiquitin-specific proteases. This structure confirms the predicted mechanism of the inhibitor and allows the direct comparison of a UCH family enzyme in the free and ligand-bound state. We also show the efficient hydrolysis by human UCH-L3 of a 13-residue peptide in isopeptide linkage with ubiquitin, consistent with considerable flexibility in UCH substrate size. We propose a model for the catalytic cycle of UCH family members which accounts for the hydrolysis of larger ubiquitin conjugates.

PubMed: 15531586
DOI: 10.1074/jbc.M410770200

Experimental method

X-RAY DIFFRACTION (1.45 Å)