2IO2

Crystal structure of human Senp2 in complex with RanGAP1-SUMO-1

Summary for 2IO2

• Entry DOI: 10.2210/pdb2io2/pdb
• Related: 1TGZ 2IO0 2IO1 2IO3
• Descriptor: Sentrin-specific protease 2, Small ubiquitin-related modifier 1, Ran GTPase-activating protein 1, ... (4 entities in total)
• Functional Keywords: sumo, ubiquitin, senp, ulp, complex, protein binding, hydrolase
• Biological source: Homo sapiens (human); More
• Cellular location: Nucleus, nuclear pore complex : Q9HC62; Nucleus membrane: P63165; Cytoplasm: P46060
• Total number of polymer chains: 3
• Total formula weight: 55486.97

Authors

Reverter, D.,Lima, C.D. (deposition date: 2006-10-09, release date: 2006-11-21, Last modification date: 2023-08-30)

Primary citation

Reverter, D.,Lima, C.D.
Structural basis for SENP2 protease interactions with SUMO precursors and conjugated substrates.
Nat.Struct.Mol.Biol., 13:1060-1068, 2006

PubMed Abstract: SUMO processing and deconjugation are essential proteolytic activities for nuclear metabolism and cell-cycle progression in yeast and higher eukaryotes. To elucidate the mechanisms used during substrate lysine deconjugation, SUMO isoform processing and SUMO isoform interactions, X-ray structures were determined for a catalytically inert SENP2 protease domain in complex with conjugated RanGAP1-SUMO-1 or RanGAP1-SUMO-2, or in complex with SUMO-2 or SUMO-3 precursors. Common features within the active site include a 90 degrees kink proximal to the scissile bond that forces C-terminal amino acid residues or the lysine side chain toward a protease surface that appears optimized for lysine deconjugation. Analysis of this surface reveals SENP2 residues, particularly Met497, that mediate, and in some instances reverse, in vitro substrate specificity. Mutational analysis and biochemistry provide a mechanism for SENP2 substrate preferences that explains why SENP2 catalyzes SUMO deconjugation more efficiently than processing.

PubMed: 17099700
DOI: 10.1038/nsmb1168

Experimental method

X-RAY DIFFRACTION (2.9 Å)