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2g4d
From Proteopedia
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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
Page seeded by OCA on Mon Nov 12 22:14:41 2007
