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" |