1yzb
From Proteopedia
(New page: 200px<br /> <applet load="1yzb" size="450" color="white" frame="true" align="right" spinBox="true" caption="1yzb" /> '''Solution structure of the Josephin domain o...) |
|||
| Line 1: | Line 1: | ||
| - | [[Image:1yzb.gif|left|200px]]<br /> | + | [[Image:1yzb.gif|left|200px]]<br /><applet load="1yzb" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="1yzb" size=" | + | |
caption="1yzb" /> | caption="1yzb" /> | ||
'''Solution structure of the Josephin domain of Ataxin-3'''<br /> | '''Solution structure of the Josephin domain of Ataxin-3'''<br /> | ||
==Overview== | ==Overview== | ||
| - | The Josephin domain plays an important role in the cellular functions of | + | The Josephin domain plays an important role in the cellular functions of ataxin-3, the protein responsible for the neurodegenerative Machado-Joseph disease. We have determined the solution structure of Josephin and shown that it belongs to the family of papain-like cysteine proteases, sharing the highest degree of structural similarity with bacterial staphopain. A currently unique structural feature of Josephin is a flexible helical hairpin formed by a 32-residue insertion, which could determine substrate specificity. By using the Josephin structure and the availability of NMR chemical shift assignments, we have mapped the enzyme active site by using the typical cysteine protease inhibitors, transepoxysuccinyl-L-eucylamido-4-guanidino-butane (E-64) and [L-3-trans-(propylcarbamyl)oxirane-2-carbonyl]-L-isoleucyl-L-proline (CA-074). We also demonstrate that the specific interaction of Josephin with the ubiquitin-like domain of the ubiquitin- and proteasome-binding factor HHR23B involves complementary exposed hydrophobic surfaces. The structural similarity with other deubiquitinating enzymes suggests a model for the proteolytic enzymatic activity of ataxin-3. |
==Disease== | ==Disease== | ||
| Line 11: | Line 10: | ||
==About this Structure== | ==About this Structure== | ||
| - | 1YZB is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http:// | + | 1YZB is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1YZB OCA]. |
==Reference== | ==Reference== | ||
| Line 17: | Line 16: | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Knowles, P | + | [[Category: Knowles, P P.]] |
[[Category: Masino, L.]] | [[Category: Masino, L.]] | ||
| - | [[Category: McDonald, N | + | [[Category: McDonald, N Q.]] |
| - | [[Category: Menon, R | + | [[Category: Menon, R P.]] |
[[Category: Nicastro, G.]] | [[Category: Nicastro, G.]] | ||
[[Category: Pastore, A.]] | [[Category: Pastore, A.]] | ||
[[Category: papain-like fold]] | [[Category: papain-like fold]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:10:40 2008'' |
Revision as of 14:10, 21 February 2008
|
Solution structure of the Josephin domain of Ataxin-3
Contents |
Overview
The Josephin domain plays an important role in the cellular functions of ataxin-3, the protein responsible for the neurodegenerative Machado-Joseph disease. We have determined the solution structure of Josephin and shown that it belongs to the family of papain-like cysteine proteases, sharing the highest degree of structural similarity with bacterial staphopain. A currently unique structural feature of Josephin is a flexible helical hairpin formed by a 32-residue insertion, which could determine substrate specificity. By using the Josephin structure and the availability of NMR chemical shift assignments, we have mapped the enzyme active site by using the typical cysteine protease inhibitors, transepoxysuccinyl-L-eucylamido-4-guanidino-butane (E-64) and [L-3-trans-(propylcarbamyl)oxirane-2-carbonyl]-L-isoleucyl-L-proline (CA-074). We also demonstrate that the specific interaction of Josephin with the ubiquitin-like domain of the ubiquitin- and proteasome-binding factor HHR23B involves complementary exposed hydrophobic surfaces. The structural similarity with other deubiquitinating enzymes suggests a model for the proteolytic enzymatic activity of ataxin-3.
Disease
Known diseases associated with this structure: Machado-Joseph disease OMIM:[607047]
About this Structure
1YZB is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
The solution structure of the Josephin domain of ataxin-3: structural determinants for molecular recognition., Nicastro G, Menon RP, Masino L, Knowles PP, McDonald NQ, Pastore A, Proc Natl Acad Sci U S A. 2005 Jul 26;102(30):10493-8. Epub 2005 Jul 14. PMID:16020535
Page seeded by OCA on Thu Feb 21 16:10:40 2008
