1xd3: Difference between revisions
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|PDB= 1xd3 |SIZE=350|CAPTION= <scene name='initialview01'>1xd3</scene>, resolution 1.45Å | |PDB= 1xd3 |SIZE=350|CAPTION= <scene name='initialview01'>1xd3</scene>, resolution 1.45Å | ||
|SITE= | |SITE= | ||
|LIGAND= <scene name='pdbligand= | |LIGAND= <scene name='pdbligand=GVE:METHYL+4-AMINOBUTANOATE'>GVE</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene> | ||
|ACTIVITY= [http://en.wikipedia.org/wiki/Ubiquitinyl_hydrolase_1 Ubiquitinyl hydrolase 1], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.19.12 3.4.19.12] | |ACTIVITY= <span class='plainlinks'>[http://en.wikipedia.org/wiki/Ubiquitinyl_hydrolase_1 Ubiquitinyl hydrolase 1], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.19.12 3.4.19.12] </span> | ||
|GENE= | |GENE= | ||
|DOMAIN= | |||
|RELATEDENTRY=[[1cmx|1CMX]], [[1ubq|1UBQ]], [[1uch|1UCH]] | |||
|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1xd3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1xd3 OCA], [http://www.ebi.ac.uk/pdbsum/1xd3 PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1xd3 RCSB]</span> | |||
}} | }} | ||
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==Overview== | ==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. | 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== | ==About this Structure== | ||
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[[Category: Ovaa, H.]] | [[Category: Ovaa, H.]] | ||
[[Category: Ploegh, H L.]] | [[Category: Ploegh, H L.]] | ||
[[Category: active site crossover loop]] | [[Category: active site crossover loop]] | ||
[[Category: enzyme-ligand complex]] | [[Category: enzyme-ligand complex]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 00:47:56 2008'' | ||
