SUMO protease SENP1 induces isomerization of the scissile peptide bond

Linnan Shen, Michael H Tatham, Changjiang Dong, Anna Zagórska, James H Naismith, Ronald T Hay

Research output: Contribution to journalArticle

90 Citations (Scopus)

Abstract

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.
Original languageEnglish
Pages (from-to)1069-77
Number of pages9
JournalNature Structural & Molecular Biology
Volume13
Issue number12
DOIs
Publication statusPublished - Dec 2006

Keywords

  • 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

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