2g4d
From Proteopedia
(New page: 200px<br /> <applet load="2g4d" size="450" color="white" frame="true" align="right" spinBox="true" caption="2g4d, resolution 2.800Å" /> '''Crystal structure ...) |
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| - | [[Image:2g4d.gif|left|200px]]<br /> | + | [[Image:2g4d.gif|left|200px]]<br /><applet load="2g4d" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="2g4d" size=" | + | |
caption="2g4d, resolution 2.800Å" /> | caption="2g4d, resolution 2.800Å" /> | ||
'''Crystal structure of human SENP1 mutant (C603S) in complex with SUMO-1'''<br /> | '''Crystal structure of human SENP1 mutant (C603S) in complex with SUMO-1'''<br /> | ||
==Overview== | ==Overview== | ||
| - | SUMO (small ubiquitin-related modifier)-specific proteases catalyse the | + | SUMO (small ubiquitin-related modifier)-specific proteases catalyse the maturation and de-conjugation processes of the sumoylation pathway and modulate various cellular responses including nuclear metabolism and cell cycle progression. The active-site cysteine residue is conserved among all known SUMO-specific proteases and is not substitutable by serine in the hydrolysis reactions demonstrated previously in yeast. We report here that the catalytic domain of human protease SENP1 (SUMO-specific protease 1) mutant SENP1C(C603S) carrying a mutation of cysteine to serine at the active site is inactive in maturation and de-conjugation reactions. To further understand the hydrolytic mechanism catalysed by SENP1, we have determined, at 2.8 A resolution (1 A = 0.1 nm), the X-ray structure of SENP1C(C603S)-SUMO-1 complex. A comparison of the structure of SENP2-SUMO-1 suggests strongly that SUMO-specific proteases require a self-conformational change prior to cleavage of peptide or isopeptide bond in the maturation and de-conjugation processes respectively. Moreover, analysis of the interface of SENP1 and SUMO-1 has led to the identification of four unique amino acids in SENP1 that facilitate the binding of SUMO-1. By means of an in vitro assay, we further demonstrate a novel function of SENP1 in hydrolysing the thioester linkage in E1-SUMO and E2-SUMO complexes. The results disclose a new mechanism of regulation of the sumoylation pathway by the SUMO-specific proteases. |
==Disease== | ==Disease== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 2G4D is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http:// | + | 2G4D is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences 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=2G4D OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Protein complex]] | [[Category: Protein complex]] | ||
| - | [[Category: Au, S | + | [[Category: Au, S W.N.]] |
| - | [[Category: Chau, S | + | [[Category: Chau, S F.]] |
| - | [[Category: Lam, K | + | [[Category: Lam, K H.]] |
[[Category: Xu, Z.]] | [[Category: Xu, Z.]] | ||
[[Category: protease]] | [[Category: protease]] | ||
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[[Category: ubiquitin-like protein]] | [[Category: ubiquitin-like protein]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 17:27:57 2008'' |
Revision as of 15:27, 21 February 2008
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Crystal structure of human SENP1 mutant (C603S) in complex with SUMO-1
Contents |
Overview
SUMO (small ubiquitin-related modifier)-specific proteases catalyse the maturation and de-conjugation processes of the sumoylation pathway and modulate various cellular responses including nuclear metabolism and cell cycle progression. The active-site cysteine residue is conserved among all known SUMO-specific proteases and is not substitutable by serine in the hydrolysis reactions demonstrated previously in yeast. We report here that the catalytic domain of human protease SENP1 (SUMO-specific protease 1) mutant SENP1C(C603S) carrying a mutation of cysteine to serine at the active site is inactive in maturation and de-conjugation reactions. To further understand the hydrolytic mechanism catalysed by SENP1, we have determined, at 2.8 A resolution (1 A = 0.1 nm), the X-ray structure of SENP1C(C603S)-SUMO-1 complex. A comparison of the structure of SENP2-SUMO-1 suggests strongly that SUMO-specific proteases require a self-conformational change prior to cleavage of peptide or isopeptide bond in the maturation and de-conjugation processes respectively. Moreover, analysis of the interface of SENP1 and SUMO-1 has led to the identification of four unique amino acids in SENP1 that facilitate the binding of SUMO-1. By means of an in vitro assay, we further demonstrate a novel function of SENP1 in hydrolysing the thioester linkage in E1-SUMO and E2-SUMO complexes. The results disclose a new mechanism of regulation of the sumoylation pathway by the SUMO-specific proteases.
Disease
Known diseases associated with this structure: Orofacial cleft 10 OMIM:[601912]
About this Structure
2G4D is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Crystal structure of the SENP1 mutant C603S-SUMO complex reveals the hydrolytic mechanism of SUMO-specific protease., Xu Z, Chau SF, Lam KH, Chan HY, Ng TB, Au SW, Biochem J. 2006 Sep 15;398(3):345-52. PMID:16712526
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