2etl
From Proteopedia
(New page: 200px<br /> <applet load="2etl" size="450" color="white" frame="true" align="right" spinBox="true" caption="2etl, resolution 2.400Å" /> '''Crystal Structure ...) |
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| - | [[Image:2etl.gif|left|200px]]<br /> | + | [[Image:2etl.gif|left|200px]]<br /><applet load="2etl" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="2etl" size=" | + | |
caption="2etl, resolution 2.400Å" /> | caption="2etl, resolution 2.400Å" /> | ||
'''Crystal Structure of Ubiquitin Carboxy-terminal Hydrolase L1 (UCH-L1)'''<br /> | '''Crystal Structure of Ubiquitin Carboxy-terminal Hydrolase L1 (UCH-L1)'''<br /> | ||
==Overview== | ==Overview== | ||
| - | The ubiquitin C-terminal hydrolase UCH-L1 (PGP9.5) comprises >1% of total | + | The ubiquitin C-terminal hydrolase UCH-L1 (PGP9.5) comprises >1% of total brain protein but is almost absent from other tissues [Wilkinson, K. D., et al. (1989) Science 246, 670-673]. Mutations in the UCH-L1 gene have been reported to be linked to susceptibility to and protection from Parkinson's disease [Leroy, E., et al. (1998) Nature 395, 451-452; Maraganore, D. M., et al. (1999) Neurology 53, 1858-1860]. Abnormal overexpression of UCH-L1 has been shown to correlate with several forms of cancer [Hibi, K., et al. (1998) Cancer Res. 58, 5690-5694]. Because the amino acid sequence of UCH-L1 is similar to that of other ubiquitin C-terminal hydrolases, including the ubiquitously expressed UCH-L3, which appear to be unconnected to neurodegenerative disease, the structure of UCH-L1 and the effects of disease associated mutations on the structure and function are of considerable importance. We have determined the three-dimensional structure of human UCH-L1 at 2.4-A resolution by x-ray crystallography. The overall fold resembles that of other ubiquitin hydrolases, including UCH-L3, but there are a number of significant differences. In particular, the geometry of the catalytic residues in the active site of UCH-L1 is distorted in such a way that the hydrolytic activity would appear to be impossible without substrate induced conformational rearrangements. |
==Disease== | ==Disease== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 2ETL is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with CL as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http:// | + | 2ETL is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=CL:'>CL</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2ETL OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Das, C.]] | [[Category: Das, C.]] | ||
| - | [[Category: Hoang, Q | + | [[Category: Hoang, Q Q.]] |
| - | [[Category: Kreinbring, C | + | [[Category: Kreinbring, C A.]] |
| - | [[Category: Lansbury, P | + | [[Category: Lansbury, P T.]] |
| - | [[Category: Luchansky, S | + | [[Category: Luchansky, S J.]] |
| - | [[Category: Meray, R | + | [[Category: Meray, R K.]] |
| - | [[Category: Petsko, G | + | [[Category: Petsko, G A.]] |
| - | [[Category: Ray, S | + | [[Category: Ray, S S.]] |
[[Category: Ringe, D.]] | [[Category: Ringe, D.]] | ||
[[Category: CL]] | [[Category: CL]] | ||
[[Category: deubiquitinating thiol hydrolase]] | [[Category: deubiquitinating thiol hydrolase]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 17:14:29 2008'' |
Revision as of 15:14, 21 February 2008
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Crystal Structure of Ubiquitin Carboxy-terminal Hydrolase L1 (UCH-L1)
Contents |
Overview
The ubiquitin C-terminal hydrolase UCH-L1 (PGP9.5) comprises >1% of total brain protein but is almost absent from other tissues [Wilkinson, K. D., et al. (1989) Science 246, 670-673]. Mutations in the UCH-L1 gene have been reported to be linked to susceptibility to and protection from Parkinson's disease [Leroy, E., et al. (1998) Nature 395, 451-452; Maraganore, D. M., et al. (1999) Neurology 53, 1858-1860]. Abnormal overexpression of UCH-L1 has been shown to correlate with several forms of cancer [Hibi, K., et al. (1998) Cancer Res. 58, 5690-5694]. Because the amino acid sequence of UCH-L1 is similar to that of other ubiquitin C-terminal hydrolases, including the ubiquitously expressed UCH-L3, which appear to be unconnected to neurodegenerative disease, the structure of UCH-L1 and the effects of disease associated mutations on the structure and function are of considerable importance. We have determined the three-dimensional structure of human UCH-L1 at 2.4-A resolution by x-ray crystallography. The overall fold resembles that of other ubiquitin hydrolases, including UCH-L3, but there are a number of significant differences. In particular, the geometry of the catalytic residues in the active site of UCH-L1 is distorted in such a way that the hydrolytic activity would appear to be impossible without substrate induced conformational rearrangements.
Disease
Known disease associated with this structure: Parkinson disease, familial OMIM:[191342]
About this Structure
2ETL is a Single protein structure of sequence from Homo sapiens with as ligand. Full crystallographic information is available from OCA.
Reference
Structural basis for conformational plasticity of the Parkinson's disease-associated ubiquitin hydrolase UCH-L1., Das C, Hoang QQ, Kreinbring CA, Luchansky SJ, Meray RK, Ray SS, Lansbury PT, Ringe D, Petsko GA, Proc Natl Acad Sci U S A. 2006 Mar 21;103(12):4675-80. Epub 2006 Mar 13. PMID:16537382
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