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Title: Structural Basis for SENP2 Protease Interactions with SUMO Precursers 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 degree 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.

Authors:
;
Publication Date:
Research Org.:
Brookhaven National Laboratory (BNL) National Synchrotron Light Source
Sponsoring Org.:
Doe - Office Of Science
OSTI Identifier:
930652
Report Number(s):
BNL-81120-2008-JA
TRN: US200901%%163
DOE Contract Number:
DE-AC02-98CH10886
Resource Type:
Journal Article
Resource Relation:
Journal Name: Nature Structural and Molecular Biology; Journal Volume: 13; Journal Issue: 12
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; AMINO ACIDS; BIOCHEMISTRY; CELL CYCLE; CHAINS; IN VITRO; LYSINE; METABOLISM; PROCESSING; RESIDUES; SPECIFICITY; SUBSTRATES; YEASTS; national synchrotron light source

Citation Formats

Reverter,D., and Lima, C. Structural Basis for SENP2 Protease Interactions with SUMO Precursers and Conjugated Substrates. United States: N. p., 2007. Web.
Reverter,D., & Lima, C. Structural Basis for SENP2 Protease Interactions with SUMO Precursers and Conjugated Substrates. United States.
Reverter,D., and Lima, C. Mon . "Structural Basis for SENP2 Protease Interactions with SUMO Precursers and Conjugated Substrates". United States. doi:.
@article{osti_930652,
title = {Structural Basis for SENP2 Protease Interactions with SUMO Precursers and Conjugated Substrates},
author = {Reverter,D. and Lima, C.},
abstractNote = {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 degree 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.},
doi = {},
journal = {Nature Structural and Molecular Biology},
number = 12,
volume = 13,
place = {United States},
year = {Mon Jan 01 00:00:00 EST 2007},
month = {Mon Jan 01 00:00:00 EST 2007}
}