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226 a.a.
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76 a.a.
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156 a.a.
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* Residue conservation analysis
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PDB id:
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Hydrolase/hydrolase activator
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Title:
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Senp1 (mutant) sumo1 rangap
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Structure:
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Sentrin-specific protease 1. Chain: a. Fragment: c-terminal fragment, residues 419-643. Synonym: senp1, sentrin/sumo-specific protease senp1. Engineered: yes. Mutation: yes. Small ubiquitin-related modifier 1. Chain: b. Synonym: sumo-1, ubiquitin-like protein smt3c, smt3 homolog 3,
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Source:
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Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 562. Expression_system_taxid: 562
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Biol. unit:
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Trimer (from PDB file)
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Resolution:
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2.77Å
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R-factor:
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0.230
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R-free:
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0.279
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Authors:
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L.Shen,C.Dong,J.H.Naismith
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Key ref:
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L.Shen
et al.
(2006).
SUMO protease SENP1 induces isomerization of the scissile peptide bond.
Nat Struct Mol Biol,
13,
1069-1077.
PubMed id:
DOI:
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Date:
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11-Jul-06
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Release date:
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07-Aug-06
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PROCHECK
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Headers
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References
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Q9P0U3
(SENP1_HUMAN) -
Sentrin-specific protease 1 from Homo sapiens
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Seq:
Struc:
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644 a.a.
226 a.a.*
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DOI no:
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Nat Struct Mol Biol
13:1069-1077
(2006)
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PubMed id:
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SUMO protease SENP1 induces isomerization of the scissile peptide bond.
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L.Shen,
M.H.Tatham,
C.Dong,
A.Zagórska,
J.H.Naismith,
R.T.Hay.
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ABSTRACT
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Small ubiquitin-like modifier (SUMO)-specific protease SENP1 processes SUMO-1,
SUMO-2 and SUMO-3 to mature forms and deconjugates them from modified proteins.
To establish the proteolytic mechanism, we determined structures of
catalytically inactive SENP1 bound to SUMO-1-modified RanGAP1 and to unprocessed
SUMO-1. In each case, the scissile peptide bond is kinked at a right angle to
the C-terminal tail of SUMO-1 and has the cis configuration of the amide
nitrogens. SENP1 preferentially processes SUMO-1 over SUMO-2, but binding
thermodynamics of full-length SUMO-1 and SUMO-2 to SENP1 and K(m) values for
processing are very similar. However, k(cat) values differ by 50-fold. Thus,
discrimination between unprocessed SUMO-1 and SUMO-2 by SENP1 is based on a
catalytic step rather than substrate binding and is likely to reflect
differences in the ability of SENP1 to correctly orientate the scissile bonds in
SUMO-1 and SUMO-2.
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Selected figure(s)
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Figure 2.
Figure 2. Structure of full-length SUMO-1 bound to SENP1 C603A.
(a) SENP1(C603A)–SUMO-1-FL complex. Cyan, SENP1; purple,
SUMO-1-FL. SENP1 is effectively identical to earlier
descriptions. (b) Superposition of
SENP1(C603A)–RanGAP1–SUMO-1 complex with
SENP1(C603A)–SUMO-1-FL complex. In the superposed
RanGAP1–SUMO-1 complex, RanGAP1 is in red, SENP1 is in dark
blue and SUMO-1 is in turquoise. Isopeptide bond is depicted as
in Figure 1a. (c) Detail of the complex in a, with SENP1 in dark
blue and carbons of SUMO-1-FL in pink. Residues mentioned in the
text are indicated. Dotted line denotes hydrogen bond. (d) The
same cis arrangement of nitrogens is seen in the
SENP1(C603A)–SUMO-1-FL processing complex and in the
SENP1(C603A)–RanGAP1–SUMO-1 deconjugating complex (colored
as in b and c).
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Figure 4.
Figure 4. Thermodynamics of substrate and product binding by
SENP1 C603A. ITC was used to study the thermodynamic changes
effected by binding of SENP1 to SUMO-1-FL, SUMO-2-FL,
RanGAP1–SUMO-1, SUMO-1-GG, SUMO-2-GG or RanGAP1 (as
indicated). Experiments were repeated on three separate
occasions with very similar results. Thermodynamic parameters
are indicated in Table 1.
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The above figures are
reprinted
by permission from Macmillan Publishers Ltd:
Nat Struct Mol Biol
(2006,
13,
1069-1077)
copyright 2006.
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Figures were
selected
by an automated process.
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Literature references that cite this PDB file's key reference
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PubMed id
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Reference
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L.D.Plant,
E.J.Dowdell,
I.S.Dementieva,
J.D.Marks,
and
S.A.Goldstein
(2011).
SUMO modification of cell surface Kv2.1 potassium channels regulates the activity of rat hippocampal neurons.
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J Gen Physiol,
137,
441-454.
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R.N.Gilbreth,
K.Truong,
I.Madu,
A.Koide,
J.B.Wojcik,
N.S.Li,
J.A.Piccirilli,
Y.Chen,
and
S.Koide
(2011).
Isoform-specific monobody inhibitors of small ubiquitin-related modifiers engineered using structure-guided library design.
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Proc Natl Acad Sci U S A,
108,
7751-7756.
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PDB code:
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E.Van Damme,
K.Laukens,
T.H.Dang,
and
X.Van Ostade
(2010).
A manually curated network of the PML nuclear body interactome reveals an important role for PML-NBs in SUMOylation dynamics.
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Int J Biol Sci,
6,
51-67.
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L.D.Plant,
I.S.Dementieva,
A.Kollewe,
S.Olikara,
J.D.Marks,
and
S.A.Goldstein
(2010).
One SUMO is sufficient to silence the dimeric potassium channel K2P1.
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Proc Natl Acad Sci U S A,
107,
10743-10748.
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N.Kolli,
J.Mikolajczyk,
M.Drag,
D.Mukhopadhyay,
N.Moffatt,
M.Dasso,
G.Salvesen,
and
K.D.Wilkinson
(2010).
Distribution and paralogue specificity of mammalian deSUMOylating enzymes.
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Biochem J,
430,
335-344.
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D.Reverter,
and
C.D.Lima
(2009).
Preparation of SUMO proteases and kinetic analysis using endogenous substrates.
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Methods Mol Biol,
497,
225-239.
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E.T.Yeh
(2009).
SUMOylation and De-SUMOylation: Wrestling with Life's Processes.
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J Biol Chem,
284,
8223-8227.
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K.Satoo,
N.N.Noda,
H.Kumeta,
Y.Fujioka,
N.Mizushima,
Y.Ohsumi,
and
F.Inagaki
(2009).
The structure of Atg4B-LC3 complex reveals the mechanism of LC3 processing and delipidation during autophagy.
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EMBO J,
28,
1341-1350.
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PDB codes:
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L.N.Shen,
M.C.Geoffroy,
E.G.Jaffray,
and
R.T.Hay
(2009).
Characterization of SENP7, a SUMO-2/3-specific isopeptidase.
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Biochem J,
421,
223-230.
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Y.Wang,
and
M.Dasso
(2009).
SUMOylation and deSUMOylation at a glance.
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J Cell Sci,
122,
4249-4252.
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Z.Xu,
H.Y.Chan,
W.L.Lam,
K.H.Lam,
L.S.Lam,
T.B.Ng,
and
S.W.Au
(2009).
SUMO proteases: redox regulation and biological consequences.
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Antioxid Redox Signal,
11,
1453-1484.
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B.H.Ha,
H.C.Ahn,
S.H.Kang,
K.Tanaka,
C.H.Chung,
and
E.E.Kim
(2008).
Structural basis for Ufm1 processing by UfSP1.
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J Biol Chem,
283,
14893-14900.
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PDB code:
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C.D.Lima,
and
D.Reverter
(2008).
Structure of the Human SENP7 Catalytic Domain and Poly-SUMO Deconjugation Activities for SENP6 and SENP7.
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J Biol Chem,
283,
32045-32055.
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PDB code:
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M.Drag,
and
G.S.Salvesen
(2008).
DeSUMOylating enzymes--SENPs.
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IUBMB Life,
60,
734-742.
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M.H.Tatham,
M.C.Geoffroy,
L.Shen,
A.Plechanovova,
N.Hattersley,
E.G.Jaffray,
J.J.Palvimo,
and
R.T.Hay
(2008).
RNF4 is a poly-SUMO-specific E3 ubiquitin ligase required for arsenic-induced PML degradation.
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Nat Cell Biol,
10,
538-546.
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A.D.Capili,
and
C.D.Lima
(2007).
Taking it step by step: mechanistic insights from structural studies of ubiquitin/ubiquitin-like protein modification pathways.
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Curr Opin Struct Biol,
17,
726-735.
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D.Mukhopadhyay,
and
M.Dasso
(2007).
Modification in reverse: the SUMO proteases.
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Trends Biochem Sci,
32,
286-295.
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D.T.Huang,
and
B.A.Schulman
(2006).
Breaking up with a kinky SUMO.
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Nat Struct Mol Biol,
13,
1045-1047.
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The most recent references are shown first.
Citation data come partly from CiteXplore and partly
from an automated harvesting procedure. Note that this is likely to be
only a partial list as not all journals are covered by
either method. However, we are continually building up the citation data
so more and more references will be included with time.
Where a reference describes a PDB structure, the PDB
code is
shown on the right.
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Links
