2G4D

Crystal structure of human SENP1 mutant (C603S) in complex with SUMO-1

Summary for 2G4D

• Entry DOI: 10.2210/pdb2g4d/pdb
• Descriptor: SENP1 protein, Small ubiquitin-related modifier 1 (3 entities in total)
• Functional Keywords: protease, ubiquitin-like protein, sumo maturation, sumo deconjugation, hydrolase-protein binding complex, hydrolase/protein binding
• Biological source: Homo sapiens (human); More
• Cellular location: Nucleus : Q9P0U3; Nucleus membrane: P63165
• Total number of polymer chains: 4
• Total formula weight: 66953.40

Authors

Xu, Z.,Chau, S.F.,Lam, K.H.,Au, S.W.N. (deposition date: 2006-02-22, release date: 2006-10-17, Last modification date: 2024-05-29)

Primary citation

Xu, Z.,Chau, S.F.,Lam, K.H.,Chan, H.Y.,Ng, T.B.,Au, S.W.N.
Crystal structure of the SENP1 mutant C603S-SUMO complex reveals the hydrolytic mechanism of SUMO-specific protease
Biochem.J., 398:345-352, 2006

PubMed Abstract: 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.

PubMed: 16712526
DOI: 10.1042/BJ20060526

Experimental method

X-RAY DIFFRACTION (2.8 Å)