SUMO protease SENP1 induces isomerization of the scissile peptide bond

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

    Research output: Contribution to journalArticle

    79 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, kcat 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 & Molecular Biology
    Volume13
    Issue number12
    DOIs
    Publication statusPublished - Dec 2006

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    Ubiquitin
    Peptide Hydrolases
    Peptides
    Thermodynamics
    Amides
    Nitrogen

    Cite this

    Shen, Linnan ; Tatham, Michael H. ; Dong, Changjiang ; Zagorska, Anna ; Naismith, James H. ; Hay, Ronald T. / SUMO protease SENP1 induces isomerization of the scissile peptide bond. In: Nature Structural & Molecular Biology. 2006 ; Vol. 13, No. 12. pp. 1069-1077.
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    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, kcat 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.",
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    SUMO protease SENP1 induces isomerization of the scissile peptide bond. / Shen, Linnan; Tatham, Michael H.; Dong, Changjiang; Zagorska, Anna; Naismith, James H.; Hay, Ronald T.

    In: Nature Structural & Molecular Biology, Vol. 13, No. 12, 12.2006, p. 1069-1077.

    Research output: Contribution to journalArticle

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    AU - Hay, Ronald T.

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