2bkq
From Proteopedia
(New page: 200px<br /> <applet load="2bkq" size="450" color="white" frame="true" align="right" spinBox="true" caption="2bkq, resolution 2.00Å" /> '''NEDD8 PROTEASE'''<b...) |
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| - | [[Image:2bkq.gif|left|200px]]<br /> | + | [[Image:2bkq.gif|left|200px]]<br /><applet load="2bkq" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="2bkq" size=" | + | |
caption="2bkq, resolution 2.00Å" /> | caption="2bkq, resolution 2.00Å" /> | ||
'''NEDD8 PROTEASE'''<br /> | '''NEDD8 PROTEASE'''<br /> | ||
==Overview== | ==Overview== | ||
| - | NEDD8 (neural precursor cell expressed developmentally downregulated gene | + | NEDD8 (neural precursor cell expressed developmentally downregulated gene 8)-specific protease NEDP1 processes preNEDD8 to its mature form and deconjugates NEDD8 from substrates such as p53 and cullins. Although NEDD8 and ubiquitin are highly related in sequence and structure, their attachment to a protein leads to different biological effects. It is therefore critical that NEDP1 discriminates between NEDD8 and ubiquitin, and this requires remarkable precision in molecular recognition. To determine the basis of this specificity, we have determined the crystal structure of NEDP1 in isolation and in a transition state complex with NEDD8. This reveals that NEDP1 is a cysteine protease of the Ulp family. Binding of NEDD8 induces a dramatic conformational change in a flexible loop that swings over the C-terminus of NEDD8 locking it into an extended beta-structure optimal for catalysis. Structural, mutational and biochemical studies have identified key residues involved in molecular recognition. A single-residue difference in the C-terminus of NEDD8 and ubiquitin contributes significantly to the ability of NEDP1 to discriminate between them. In vivo analysis indicates that NEDP1 mutants perturb deNEDDylation of the tumour suppressor p53. |
==About this Structure== | ==About this Structure== | ||
| - | 2BKQ 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:// | + | 2BKQ 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=2BKQ OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Dong, C.]] | [[Category: Dong, C.]] | ||
| - | [[Category: Hay, R | + | [[Category: Hay, R T.]] |
[[Category: Liu, H.]] | [[Category: Liu, H.]] | ||
| - | [[Category: Naismith, J | + | [[Category: Naismith, J H.]] |
| - | [[Category: Shen, L | + | [[Category: Shen, L N.]] |
[[Category: Xirodimas, D.]] | [[Category: Xirodimas, D.]] | ||
[[Category: hydrolase]] | [[Category: hydrolase]] | ||
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[[Category: ubl conjugation pathway]] | [[Category: ubl conjugation pathway]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:38:49 2008'' |
Revision as of 14:38, 21 February 2008
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NEDD8 PROTEASE
Overview
NEDD8 (neural precursor cell expressed developmentally downregulated gene 8)-specific protease NEDP1 processes preNEDD8 to its mature form and deconjugates NEDD8 from substrates such as p53 and cullins. Although NEDD8 and ubiquitin are highly related in sequence and structure, their attachment to a protein leads to different biological effects. It is therefore critical that NEDP1 discriminates between NEDD8 and ubiquitin, and this requires remarkable precision in molecular recognition. To determine the basis of this specificity, we have determined the crystal structure of NEDP1 in isolation and in a transition state complex with NEDD8. This reveals that NEDP1 is a cysteine protease of the Ulp family. Binding of NEDD8 induces a dramatic conformational change in a flexible loop that swings over the C-terminus of NEDD8 locking it into an extended beta-structure optimal for catalysis. Structural, mutational and biochemical studies have identified key residues involved in molecular recognition. A single-residue difference in the C-terminus of NEDD8 and ubiquitin contributes significantly to the ability of NEDP1 to discriminate between them. In vivo analysis indicates that NEDP1 mutants perturb deNEDDylation of the tumour suppressor p53.
About this Structure
2BKQ is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Structural basis of NEDD8 ubiquitin discrimination by the deNEDDylating enzyme NEDP1., Shen LN, Liu H, Dong C, Xirodimas D, Naismith JH, Hay RT, EMBO J. 2005 Apr 6;24(7):1341-51. Epub 2005 Mar 17. PMID:15775960
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