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PDBsum entry 2io2
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Protein binding, hydrolase
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PDB id
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2io2
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Contents |
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225 a.a.
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75 a.a.
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156 a.a.
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References listed in PDB file
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Key reference
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Title
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Structural basis for senp2 protease interactions with sumo precursors and conjugated substrates.
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Authors
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D.Reverter,
C.D.Lima.
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Ref.
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Nat Struct Mol Biol, 2006,
13,
1060-1068.
[DOI no: ]
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PubMed id
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Abstract
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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 degrees 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.
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Figure 1.
Figure 1. Structures of SENP2 deconjugation complexes with
RanGAP1–SUMO-1 and RanGAP1–SUMO-2. (a) Two nearly
orthogonal views of the human SENP2 catalytic domain in complex
with the C-terminal domain of RanGAP1 conjugated to either
SUMO-2 (left) or SUMO-1 (right), shown as ribbons. SENP2
catalytic residues are shown in bond representation, as is the
isopeptide bond between lysine and the SUMO diglycine motif. (b)
Stereo representation of the interaction between the SUMO-1
C-terminal tail (yellow), SENP2 (blue) and the consensus
residues of RanGAP1 (magenta), with interacting residues labeled
and shown in bond representation. Red dashed lines denote
putative hydrogen bonds. (c) Surface representation of SENP2 in
complex with the consensus residues of RanGAP1 conjugated to the
SUMO-1 diglycine motif. SUMO-1 C-terminal residues (yellow) and
RanGAP1 consensus motif (magenta) are shown as sticks. (d)
Stereo view of Ubc9 (SUMO E2, yellow) active site in complex
with RanGAP1–SUMO-1 (PDB 1Z5S)^29, depicted as in b. (e)
Simulated annealing omit map contoured at 1.2  ,
covering the isopeptide bond and selected active site residues
in the SENP2–RanGAP1–SUMO-1 structure. Graphics prepared
with PyMOL^41 (http://pymol.sourceforge.net).
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Figure 5.
Figure 5. Comparison of the hydrogen bond coordination of the
 and
 peptide
bonds in the deconjugation and processing complexes. (a)
Stick representation of isopeptide bond between RanGAP1 Lys524
and SUMO Gly97. Blue, SENP2; yellow, SUMO; magenta, RanGAP1; red
dashed lines, hydrogen bonds. (b) Stick representation of
scissile peptide bond between Gly92 and Val93 from pre-SUMO-3,
in similar orientation as in a.
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The above figures are
reprinted
by permission from Macmillan Publishers Ltd:
Nat Struct Mol Biol
(2006,
13,
1060-1068)
copyright 2006.
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