2HKP

SUMO protease Ulp1 with the catalytic cysteine oxidized to a sulfenic acid

Summary for 2HKP

• Entry DOI: 10.2210/pdb2hkp/pdb
• Related: 1euv
• Descriptor: Ubiquitin-like-specific protease 1 (2 entities in total)
• Functional Keywords: hydrolase
• Biological source: Saccharomyces cerevisiae (baker's yeast)
• Total number of polymer chains: 1
• Total formula weight: 25666.30

Authors

Xu, Z.,Ng, T.B.,Au, S.W.N. (deposition date: 2006-07-05, release date: 2007-07-31, Last modification date: 2023-10-25)

Primary citation

Xu, Z.,Lam, L.S.M.,Lam, L.H.,Chau, S.F.,Ng, T.B.,Au, S.W.N.
Molecular basis of the redox regulation of SUMO proteases: a protective mechanism of intermolecular disulfide linkage against irreversible sulfhydryl oxidation
Faseb J., 22:127-137, 2008

PubMed Abstract: Sumoylation has emerged as an indispensable post-translational modification that modulates the functions of a broad spectrum of proteins. Recent studies have demonstrated that reactive oxygen species influence the equilibrium of sumoylation-desumoylation. We show herein that H2O2 induces formation of an intermolecular disulfide linkage of human SUMO protease SENP1 via the active-site Cys 603 and a unique residue Cys 613. Such reversible modification confers a higher recovery of enzyme activity, which is also observed in yeast Ulp1, but not in human SENP2, suggesting its protective role against irreversible sulfhydryl oxidation. In vivo formation of a disulfide-linked dimer of SENP1 is also detected in cultured cells in response to oxidative stress. The modifications are further elucidated by the crystal structures of Ulp1 with the catalytic cysteine oxidized to sulfenic, sulfinic, and sulfonic acids. Our findings suggest that, in addition to SUMO conjugating enzymes, SUMO proteases may act as redox sensors and effectors modulating the desumoylation pathway and specific cellular responses to oxidative stress.

PubMed: 17704192
DOI: 10.1096/fj.06-7871com

Experimental method

X-RAY DIFFRACTION (2.1 Å)