| Autor: |
Xu Z; Department of Biochemistry and Molecular Biotechnology Program, Centre for Protein Science and Crystallography, Faculty of Science, The Chinese University of Hong Kong, Shatin, Hong Kong., Chau SF, Lam KH, Chan HY, Ng TB, Au SW |
| Jazyk: |
angličtina |
| Zdroj: |
The Biochemical journal [Biochem J] 2006 Sep 15; Vol. 398 (3), pp. 345-52. |
| DOI: |
10.1042/BJ20060526 |
| Abstrakt: |
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. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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