Structural basis for SENP2 protease interactions with SUMO precursors and conjugated substrates Journal Article

  


Authors: Reverter, D.; Lima, C. D.
Article Title: Structural basis for SENP2 protease interactions with SUMO precursors and conjugated substrates
Abstract: SUMO processing and deconjugation are essential proteolytic activities for nuclear metabolism and cell-cycle progression in yeast and higher eukaryotes. To elucidate the mechanisms used during substrate lysine deconjugation, SUMO isoform processing and SUMO isoform interactions, X-ray structures were determined for a catalytically inert SENP2 protease domain in complex with conjugated RanGAP1-SUMO-1 or RanGAP1-SUMO-2, or in complex with SUMO-2 or SUMO-3 precursors. Common features within the active site include a 90° kink proximal to the scissile bond that forces C-terminal amino acid residues or the lysine side chain toward a protease surface that appears optimized for lysine deconjugation. Analysis of this surface reveals SENP2 residues, particularly Met497, that mediate, and in some instances reverse, in vitro substrate specificity. Mutational analysis and biochemistry provide a mechanism for SENP2 substrate preferences that explains why SENP2 catalyzes SUMO deconjugation more efficiently than processing. © 2006 Nature Publishing Group.
Keywords: mutation; cell cycle; protein degradation; protein binding; protein interaction; in vitro study; mutational analysis; eukaryota; substrate specificity; gtpase-activating proteins; hydrogen bonding; models, molecular; crystallography, x-ray; protein structure, tertiary; proteinase; yeast; protein structure; enzyme specificity; protein structure, quaternary; lysine; structural homology, protein; small ubiquitin-related modifier proteins; protein precursors; sumo 1 protein; cysteine endopeptidases; senp2 protease
Journal Title: Nature Structural and Molecular Biology
Volume: 13
Issue: 12
ISSN: 1545-9993
Publisher: Nature Publishing Group  
Date Published: 2006-12-01
Start Page: 1060
End Page: 1068
Language: English
DOI: 10.1038/nsmb1168
PUBMED: 17099700
PROVIDER: scopus
DOI/URL:

http://www.scopus.com/inward/record.url?eid=2-s2.0-33845370047&partnerID=40&md5=5ce19449b69652a30c48a72e377f371d
Notes: --- - "Cited By (since 1996): 44" - "Export Date: 4 June 2012" - "CODEN: NSMBC" - "Source: Scopus"
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MSK Authors
  1. David Reverter
    7 Reverter
  2. Christopher D Lima
    103 Lima
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