1xd3
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(New page: 200px<br /> <applet load="1xd3" size="450" color="white" frame="true" align="right" spinBox="true" caption="1xd3, resolution 1.45Å" /> '''Crystal structure o...)
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Revision as of 17:57, 12 November 2007
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Crystal structure of UCHL3-UbVME complex
Overview
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.
About this Structure
1XD3 is a Protein complex structure of sequences from Homo sapiens with MG and GVE as ligands. Active as Ubiquitinyl hydrolase 1, with EC number 3.4.19.12 Full crystallographic information is available from OCA.
Reference
Structure of the ubiquitin hydrolase UCH-L3 complexed with a suicide substrate., Misaghi S, Galardy PJ, Meester WJ, Ovaa H, Ploegh HL, Gaudet R, J Biol Chem. 2005 Jan 14;280(2):1512-20. Epub 2004 Nov 5. PMID:15531586
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