1xd3: Difference between revisions

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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"

<applet load="1xd3" size="~~450~~" color="white" frame="true" align="right" spinBox="true"

caption="1xd3, resolution 1.45Å" />

'''Crystal structure of UCHL3-UbVME complex'''<br />

==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.

==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==

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://~~ispc~~.weizmann.ac.il/oca-bin/ocashort?id=1XD3 OCA].

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==

Line 15:

Line 17:

[[Category: Protein complex]]

[[Category: Ubiquitinyl hydrolase 1]]

[[Category: Galardy, P.J.]]

[[Category: Galardy, P J.]]

[[Category: Gaudet, R.]]

[[Category: Meester, W.J.N.]]

[[Category: Meester, W J.N.]]

[[Category: Misaghi, S.]]

[[Category: Ovaa, H.]]

[[Category: Ploegh, H.L.]]

[[Category: Ploegh, H L.]]

[[Category: GVE]]

[[Category: MG]]

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[[Category: enzyme-ligand complex]]

''Page seeded by [http://~~ispc~~.weizmann.ac.il/oca OCA ] on ~~Mon Nov 12 20~~:03:~~52 2007~~''

''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 15:53:32 2008''

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@@ Line 1: / Line 1: @@
-[[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"
-<applet load="1xd3" size="450" color="white" frame="true" align="right" spinBox="true"
 caption="1xd3, resolution 1.45&Aring;" />
 '''Crystal structure of UCHL3-UbVME complex'''<br />
 ==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.
+==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==
-XD3 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://ispc.weizmann.ac.il/oca-bin/ocashort?id=1XD3 OCA].
+XD3 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==
@@ Line 15: / Line 17: @@
 [[Category: Protein complex]]
 [[Category: Ubiquitinyl hydrolase 1]]
-[[Category: Galardy, P.J.]]
+[[Category: Galardy, P J.]]
 [[Category: Gaudet, R.]]
-[[Category: Meester, W.J.N.]]
+[[Category: Meester, W J.N.]]
 [[Category: Misaghi, S.]]
 [[Category: Ovaa, H.]]
-[[Category: Ploegh, H.L.]]
+[[Category: Ploegh, H L.]]
 [[Category: GVE]]
 [[Category: MG]]
@@ Line 26: / Line 28: @@
 [[Category: enzyme-ligand complex]]
-''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 12 20:03:52 2007''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 15:53:32 2008''