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PDBsum entry 2iy0
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Hydrolase/hydrolase activator
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PDB id
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2iy0
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Contents |
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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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References listed in PDB file
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Key reference
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Title
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Sumo protease senp1 induces isomerization of the scissile peptide bond.
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Authors
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L.Shen,
M.H.Tatham,
C.Dong,
A.Zagórska,
J.H.Naismith,
R.T.Hay.
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Ref.
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Nat Struct Mol Biol, 2006,
13,
1069-1077.
[DOI no: ]
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PubMed id
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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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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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