2g4d
Crystal structure of human SENP1 mutant (C603S) in complex with SUMO-1Crystal structure of human SENP1 mutant (C603S) in complex with SUMO-1
Structural highlights
FunctionSENP1_HUMAN Protease that catalyzes two essential functions in the SUMO pathway: processing of full-length SUMO1, SUMO2 and SUMO3 to their mature forms and deconjugation of SUMO1, SUMO2 and SUMO3 from targeted proteins. Deconjugates SUMO1 from HIPK2. Deconjugates SUMO1 from HDAC1, which decreases its transcriptional repression activity.[1] [2] [3] [4] Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedSUMO (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. 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[5] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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