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PDBsum entry 3eay
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References listed in PDB file
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Key reference
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Title
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Structure of the human senp7 catalytic domain and poly-Sumo deconjugation activities for senp6 and senp7.
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Authors
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C.D.Lima,
D.Reverter.
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Ref.
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J Biol Chem, 2008,
283,
32045-32055.
[DOI no: ]
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PubMed id
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Abstract
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Small ubiquitin-like modifier (SUMO) proteases regulate the abundance and
lifetime of SUMO-conjugated substrates by antagonizing reactions catalyzed by
SUMO-conjugating enzymes. Six SUMO proteases 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
2.4A. 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.
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Figure 3.
Structure of the catalytic domain of SENP7. A, two views of
the SENP7 catalytic domain shown in ribbon representation.
Secondary structure elements are either numbered (β-strands) or
lettered (α-helices). The catalytic residues are depicted in
stick representation near the top of each panel, and the
catalytic cysteine is labeled (C926). The insertion elements
(Loop-1, Loop-2, Loop-3, and Loop-4) are labeled in at least one
of the two panels. Segments of the polypeptide not observed in
the electron density maps were deemed disordered and are
indicated by dashed lines. The N and C termini are labeled N or
C, respectively. B, superposition of the SENP7 and SENP2 (PDB
1THO) structures in ribbon representation with SENP7 colored
blue and SENP2 colored yellow. Catalytic residues are shown in
stick representation as in A. C, superposition of SENP1 (PDB
2IYC) with SENP2 (PDB 1THO) in ribbon representation with SENP1
colored green and SENP2 colored yellow. Catalytic residues are
shown in stick representation. D, alignment of sequences
corresponding to the catalytic domains for human SENP7, SENP6,
SENP1, SENP2, and SENP3 based on structural alignment of human
SENP2 and SENP7. Gaps are denoted by dots and the large sequence
insertion within Loop-3 is depicted by // to indicate that the
sequence is missing from the alignment. Numbering above the
sequence alignment corresponds to the amino acid position in
full-length SENP7. Secondary structural elements are indicated
above the alignment for SENP7 (blue) and below the alignment for
SENP2 (yellow). For SENP7, β-strands are numbered, α-helices
lettered, and coil depicted as a line. Missing regions in our
structure are denoted by dashed lines, and the gap in Loop-3 is
indicated by //. Side chain identity (75% conservation) is
denoted in the alignment by a yellow background. Conserved
catalytic residues are depicted in red. Graphics were prepared
with PYMOL (47).
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Figure 4.
Structural models for interactions between SENP7 and SUMO. A,
superposition of the SENP7 and SENP2 catalytic domains in blue
ribbon and yellow stick representation, respectively. The
position of SUMO is indicated schematically based on the
position of SUMO2 in complex with SENP2 (PDB 2IO0). Several
residues within the SUMO-protease interface are highlighted in
stick representation and labeled according to their position and
side chain composition in SENP7. B, top panel, the structure of
SUMO2-RanGAP1 (stick and transparent surface representation) is
shown in complex with SENP2 (yellow ribbon representation) to
indicate the position of SUMO in site A (green) and the
substrate RanGAP1 in site B (pink). The bottom panel depicts the
SENP7 catalytic domain in a similar orientation to SENP2 in the
top panel to highlight the positions of Loop-2, Loop-3, and
Loop-4 with respect to the putative SUMO interaction surfaces in
site A, site B, and site C. C, close-up view of the interface
between SENP2 (yellow) and SUMO2 (green) with SENP7 (blue) shown
at the right in an analogous orientation to highlight residues
involved in interactions with SUMO at site A. D, similar to C,
but depicting the other side of the SENP2-SUMO2 complex to
highlight residues in SENP7 Loop-1 that may contribute to SUMO
interaction. E, electrostatic potential surface representation
for SENP1, SENP2, and SENP7 to highlight similarities between
SENP1 and SENP2 within the SUMO interaction surface (site A) and
the differences between SENP7 and either SENP1 or SENP2 in the
analogous surface. The relative position for SUMO in site A is
indicated by a green circle as derived from structures of
SENP1-SUMO, SENP2-SUMO and models for SENP7-SUMO.
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The above figures are
reprinted
from an Open Access publication published by the ASBMB:
J Biol Chem
(2008,
283,
32045-32055)
copyright 2008.
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