1xd3
From Proteopedia
(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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| - | [[Image:1xd3.gif|left|200px]]<br /> | + | [[Image:1xd3.gif|left|200px]]<br /><applet load="1xd3" size="350" color="white" frame="true" align="right" spinBox="true" |
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caption="1xd3, resolution 1.45Å" /> | caption="1xd3, resolution 1.45Å" /> | ||
'''Crystal structure of UCHL3-UbVME complex'''<br /> | '''Crystal structure of UCHL3-UbVME complex'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Ubiquitin C-terminal hydrolases (UCHs) comprise a family of small | + | 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. |
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| + | ==Disease== | ||
| + | Known disease associated with this structure: Cleft palate, isolated OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=191339 191339]] | ||
==About this Structure== | ==About this Structure== | ||
| - | 1XD3 is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with MG and GVE as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [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] Full crystallographic information is available from [http:// | + | 1XD3 is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=MG:'>MG</scene> and <scene name='pdbligand=GVE:'>GVE</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [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] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1XD3 OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Protein complex]] | [[Category: Protein complex]] | ||
[[Category: Ubiquitinyl hydrolase 1]] | [[Category: Ubiquitinyl hydrolase 1]] | ||
| - | [[Category: Galardy, P | + | [[Category: Galardy, P J.]] |
[[Category: Gaudet, R.]] | [[Category: Gaudet, R.]] | ||
| - | [[Category: Meester, W | + | [[Category: Meester, W J.N.]] |
[[Category: Misaghi, S.]] | [[Category: Misaghi, S.]] | ||
[[Category: Ovaa, H.]] | [[Category: Ovaa, H.]] | ||
| - | [[Category: Ploegh, H | + | [[Category: Ploegh, H L.]] |
[[Category: GVE]] | [[Category: GVE]] | ||
[[Category: MG]] | [[Category: MG]] | ||
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[[Category: enzyme-ligand complex]] | [[Category: enzyme-ligand complex]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 15:53:32 2008'' |
Revision as of 13:53, 21 February 2008
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Crystal structure of UCHL3-UbVME complex
Contents |
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.
Disease
Known disease associated with this structure: Cleft palate, isolated OMIM:[191339]
About this Structure
1XD3 is a Protein complex structure of sequences from Homo sapiens with and 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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