SUMO protease SENP1 induces isomerisation of the scissile peptide bond

LN Shen, MH Tatham, C Dong, A Zagorska, James Henderson Naismith, RT Hay

Research output: Contribution to journalArticlepeer-review

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 Km 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)1069-1077
Number of pages9
JournalNature Structural and Molecular Biology
Volume13
Issue number12
DOIs
Publication statusPublished - Dec 2006

Keywords

  • CRYSTAL-STRUCTURE
  • STRUCTURAL BASIS
  • ENERGY-TRANSFER
  • COMPLEX
  • FAMILY
  • ENZYME
  • UBC9
  • PROTEINS
  • REVEALS
  • NEDD8

Fingerprint

Dive into the research topics of 'SUMO protease SENP1 induces isomerisation of the scissile peptide bond'. Together they form a unique fingerprint.
  • BBSRC BBS/B/14426: SPORT

    Naismith, J.

    BBSRC

    18/10/0430/04/12

    Project: Standard

Cite this