Nature Structural & Molecular Biology
- 13, 1069 - 1077 (2006)
Published online: 12 November 2006; | doi:10.1038/nsmb1172
SUMO protease SENP1 induces isomerization of the scissile peptide bondLinnan Shen1, 3, Michael H Tatham1, 3, Changjiang Dong2, 3, Anna Zagórska1, James H Naismith2 & Ronald T Hay11
Centre for Interdisciplinary Research, School of Life Science, University of Dundee, DD1 5EH, UK. 2
Centre for Biomolecular Sciences, The University of St Andrews, KY16 9ST, UK. 3
These authors contributed equally to this work.
Correspondence should be addressed to James H Naismith naismith@st-andrews.ac.uk or Ronald T Hay r.t.hay@dundee.ac.uk 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.
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