SUMO protease SENP1 induces isomerization of the scissile peptide bond.
Small ubiquitin-like modifier (SUMO)-specific protease SENP1 processes SUMO-1, SUMO-2 and SUMO-3 to mature forms and deconjugates them from modified proteins. To establish the proteolytic mechanism, we determined structures of catalytically inactive SENP1 bound to SUMO-1-modified RanGAP1 and to unprocessed SUMO-1. In each case, the scissile peptide bond is kinked at ... a right angle to the C-terminal tail of SUMO-1 and has the cis configuration of the amide nitrogens. SENP1 preferentially processes SUMO-1 over SUMO-2, but binding thermodynamics of full-length SUMO-1 and SUMO-2 to SENP1 and K(m) values for processing are very similar. However, k(cat) values differ by 50-fold. Thus, discrimination between unprocessed SUMO-1 and SUMO-2 by SENP1 is based on a catalytic step rather than substrate binding and is likely to reflect differences in the ability of SENP1 to correctly orientate the scissile bonds in SUMO-1 and SUMO-2.
Mesh Terms:
Catalysis, Crystallography, X-Ray, Cysteine, Endopeptidases, GTPase-Activating Proteins, Humans, Isoenzymes, Kinetics, Models, Molecular, Peptides, Protein Binding, Protein Structure, Quaternary, SUMO-1 Protein, Substrate Specificity, Thermodynamics
Catalysis, Crystallography, X-Ray, Cysteine, Endopeptidases, GTPase-Activating Proteins, Humans, Isoenzymes, Kinetics, Models, Molecular, Peptides, Protein Binding, Protein Structure, Quaternary, SUMO-1 Protein, Substrate Specificity, Thermodynamics
Nat. Struct. Mol. Biol.
Date: Dec. 01, 2006
PubMed ID: 17099698
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