2hd5
From Proteopedia
(New page: 200px<br /> <applet load="2hd5" size="450" color="white" frame="true" align="right" spinBox="true" caption="2hd5, resolution 1.850Å" /> '''USP2 in complex wi...) |
|||
| Line 1: | Line 1: | ||
| - | [[Image:2hd5.gif|left|200px]]<br /> | + | [[Image:2hd5.gif|left|200px]]<br /><applet load="2hd5" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="2hd5" size=" | + | |
caption="2hd5, resolution 1.850Å" /> | caption="2hd5, resolution 1.850Å" /> | ||
'''USP2 in complex with ubiquitin'''<br /> | '''USP2 in complex with ubiquitin'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Deubiquitinating proteases reverse protein ubiquitination and rescue their | + | Deubiquitinating proteases reverse protein ubiquitination and rescue their target proteins from destruction by the proteasome. USP2, a cysteine protease and a member of the ubiquitin specific protease family, is overexpressed in prostate cancer and stabilizes fatty acid synthase, which has been associated with the malignancy of some aggressive prostate cancers. Here, we report the structure of the human USP2 catalytic domain in complex with ubiquitin. Ubiquitin uses two major sites for the interaction with the protease. Both sites are required simultaneously, as shown by USP2 inhibition assays with peptides and ubiquitin mutants. In addition, a layer of ordered water molecules mediates key interactions between ubiquitin and USP2. As several of those molecules are found at identical positions in the previously solved USP7/ubiquitin-aldehyde complex structure, we suggest a general mechanism of water-mediated ubiquitin recognition by USPs. |
==About this Structure== | ==About this Structure== | ||
| - | 2HD5 is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Bos_taurus Bos taurus] and [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with ZN as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/Ubiquitin_thiolesterase Ubiquitin thiolesterase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.2.15 3.1.2.15] Full crystallographic information is available from [http:// | + | 2HD5 is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Bos_taurus Bos taurus] and [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=ZN:'>ZN</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/Ubiquitin_thiolesterase Ubiquitin thiolesterase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.2.15 3.1.2.15] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2HD5 OCA]. |
==Reference== | ==Reference== | ||
| Line 23: | Line 22: | ||
[[Category: substrate enzyme complex]] | [[Category: substrate enzyme complex]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 17:40:37 2008'' |
Revision as of 15:40, 21 February 2008
|
USP2 in complex with ubiquitin
Overview
Deubiquitinating proteases reverse protein ubiquitination and rescue their target proteins from destruction by the proteasome. USP2, a cysteine protease and a member of the ubiquitin specific protease family, is overexpressed in prostate cancer and stabilizes fatty acid synthase, which has been associated with the malignancy of some aggressive prostate cancers. Here, we report the structure of the human USP2 catalytic domain in complex with ubiquitin. Ubiquitin uses two major sites for the interaction with the protease. Both sites are required simultaneously, as shown by USP2 inhibition assays with peptides and ubiquitin mutants. In addition, a layer of ordered water molecules mediates key interactions between ubiquitin and USP2. As several of those molecules are found at identical positions in the previously solved USP7/ubiquitin-aldehyde complex structure, we suggest a general mechanism of water-mediated ubiquitin recognition by USPs.
About this Structure
2HD5 is a Protein complex structure of sequences from Bos taurus and Homo sapiens with as ligand. Active as Ubiquitin thiolesterase, with EC number 3.1.2.15 Full crystallographic information is available from OCA.
Reference
Structural basis of ubiquitin recognition by the deubiquitinating protease USP2., Renatus M, Parrado SG, D'Arcy A, Eidhoff U, Gerhartz B, Hassiepen U, Pierrat B, Riedl R, Vinzenz D, Worpenberg S, Kroemer M, Structure. 2006 Aug;14(8):1293-302. PMID:16905103
Page seeded by OCA on Thu Feb 21 17:40:37 2008
