Structure of the human SENP7 catalytic domain and poly-SUMO deconjugation activities for SENP6 and SENP7 Journal Article


Authors: Lima, C. D.; Reverter, D.
Article Title: Structure of the human SENP7 catalytic domain and poly-SUMO deconjugation activities for SENP6 and SENP7
Abstract: Small ubiquitin-like modifier (SUMO) proteases regulate the abundance and lifetime of SUMO-conjugated substrates by antagonizing reactions catalyzed by SUMO-conjugating enzymes. SixSUMOproteases constitute the human SENP/ULP protease family (SENP1-3 and SENP5-7). SENP6 and SENP7 include the most divergent class of SUMO proteases, which also includes the yeast enzyme ULP2. We present the crystal structure of the SENP7 catalytic domain at a resolution of 2.4 Å. Comparison with structures of human SENP1 and SENP2 reveals unique elements that differ from previously characterized structures of SUMO-deconjugating enzymes. Biochemical assays show that SENP6 and SENP7 prefer SUMO2 or SUMO3 in deconjugation reactions with rates comparable with those catalyzed by SENP2, particularly during cleavage of di-SUMO2, di-SUMO3, and poly-SUMO chains composed of SUMO2 or SUMO3. In contrast, SENP6 and SENP7 exhibit lower rates for processing pre-SUMO1, pre-SUMO2, or pre-SUMO3 in comparison with SENP2. Structure-guided mutational analysis reveals elements unique to the SENP6 and SENP7 subclass of SENP/ULP proteases that contribute to protease function during deconjugation of poly-SUMO chains. © 2008 by The American Society for Biochemistry and Molecular Biology, Inc.
Keywords: unclassified drug; mutation; ubiquitin; chemical analysis; protein domain; proteins; protein binding; mutational analysis; protein processing; amino acid sequence; molecular sequence data; sequence alignment; crystal structure; models, molecular; crystallography, x-ray; proteinase; protein structure; protein family; sumo-1 protein; catalytic domain; reaction analysis; enzymes; protein cleavage; deconjugation; endopeptidases; catalytic domains; sumo 1 protein; sumo 2 protein; sumo 3 protein; catalysts; cysteine endopeptidases; biochemical assays; deconjugation activities; life-times; unique elements; senp1 protein; senp2 protein; senp6 protein; senp7 protein
Journal Title: Journal of Biological Chemistry
Volume: 283
Issue: 46
ISSN: 0021-9258
Publisher: American Society for Biochemistry and Molecular Biology  
Date Published: 2008-11-14
Start Page: 32045
End Page: 32055
Language: English
DOI: 10.1074/jbc.M805655200
PUBMED: 18799455
PROVIDER: scopus
PMCID: PMC2581585
DOI/URL:
Notes: --- - "Cited By (since 1996): 23" - "Export Date: 17 November 2011" - "CODEN: JBCHA" - "Molecular Sequence Numbers: SWISSPROT: P55854, P61956, P63165;" - "Source: Scopus"
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  1. Christopher D Lima
    103 Lima