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* Residue conservation analysis
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Enzyme class:
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E.C.3.1.3.48
- Protein-tyrosine-phosphatase.
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Reaction:
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Protein tyrosine phosphate + H2O = protein tyrosine + phosphate
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Protein tyrosine phosphate
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+
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H(2)O
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=
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protein tyrosine
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+
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phosphate
Bound ligand (Het Group name = )
corresponds exactly
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Molecule diagrams generated from .mol files obtained from the
KEGG ftp site
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Gene Ontology (GO) functional annotation
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Cellular component
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virion
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2 terms
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Biological process
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peptidyl-tyrosine dephosphorylation
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5 terms
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Biochemical function
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hydrolase activity
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5 terms
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DOI no:
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J Biol Chem
284:10129-10137
(2009)
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PubMed id:
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Dimeric quaternary structure of the prototypical dual specificity phosphatase VH1.
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A.C.Koksal,
J.D.Nardozzi,
G.Cingolani.
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ABSTRACT
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The Vaccinia virus H1 gene product, VH1, is a dual specificity phosphatase that
down-regulates the cellular antiviral response by dephosphorylating STAT1. The
crystal structure of VH1, determined at 1.32 A resolution, reveals a novel
dimeric quaternary structure, which exposes two active sites spaced
approximately 39 A away from each other. VH1 forms a stable dimer via an
extensive domain swap of the N-terminal helix (residues 1-20). In vitro, VH1 can
dephosphorylate activated STAT1, in a reaction that is competed by the nuclear
transport adapter importin alpha5. Interestingly, VH1 is inactive with respect
to STAT1 bound to DNA, suggesting that the viral phosphatase acts predominantly
on the cytoplasmic pool of activated STAT1. We propose that the dimeric
quaternary structure of VH1 is essential for specific recognition of activated
STAT1, which prevents its nuclear translocation, thus blocking interferon-gamma
signal transduction and antiviral response.
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Selected figure(s)
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Figure 3.
Structural view of the two binding determinants stabilizing
the VH1 dimerization interface. A, six residues on the surface
of helix α1, Lys^8/Ser^14/Thr^15 and Tyr^9/Leu^13/Leu^14 engage
in extensive electrostatic and hydrophobic contacts,
respectively, with the other VH1 protomer. Only the
electrostatic contacts made by Lys^8/Ser^14/Thr^15 are shown in
a as dashed black lines. B, the interface involving α5 helices
of both protomers consists of three hydrophobic contacts that
spans beneath the two N-terminal α1 helices of the VH1 dimer.
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Figure 6.
Model for VH1-mediated dephosphorylation of activated STAT1.
A, activated STAT1 adopts a parallel conformation stabilized by
interactions of the Tyr(P)^701 with the SH2 domains (33). L,
linker; DBD, DNA-binding domain; CC, coiled-coil domain; N,
N-terminal domain; P, phosphate on Tyr^701. B, dimeric VH1 is
active with respect to this conformation of activated STAT1,
which we hypothesize exists in the cytoplasm. C, upon
dephosphorylation, STAT1 adopts a dimeric antiparallel
conformation stabilized by reciprocal interactions of the
N-terminal domains (33). D, as an alternative route, activated
STAT1 can be imported into the cell nucleus by a heterodimer of
importin α5 and importin β, where it binds to specific
promoter sequences. As demonstrated in this paper, the structure
of STAT1 bound to DNA is not accessible by VH1, probably due to
the poor accessibility of the Tyr(P)s buried against the SH2
domains (29).
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The above figures are
reprinted
by permission from the ASBMB:
J Biol Chem
(2009,
284,
10129-10137)
copyright 2009.
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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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G.T.Lountos,
J.E.Tropea,
and
D.S.Waugh
(2011).
Structure of human dual-specificity phosphatase 27 at 2.38 Å resolution.
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Acta Crystallogr D Biol Crystallogr, 67,
471-479.
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PDB code:
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C.W.Vander Kooi,
A.O.Taylor,
R.M.Pace,
D.A.Meekins,
H.F.Guo,
Y.Kim,
and
M.S.Gentry
(2010).
Structural basis for the glucan phosphatase activity of Starch Excess4.
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Proc Natl Acad Sci U S A, 107,
15379-15384.
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PDB code:
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J.D.Nardozzi,
K.Lott,
and
G.Cingolani
(2010).
Phosphorylation meets nuclear import: a review.
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Cell Commun Signal, 8,
32.
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K.Van Vliet,
M.R.Mohamed,
L.Zhang,
N.Y.Villa,
S.J.Werden,
J.Liu,
and
G.McFadden
(2009).
Poxvirus proteomics and virus-host protein interactions.
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Microbiol Mol Biol Rev, 73,
730-749.
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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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