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PDBsum entry 1yts
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References listed in PDB file
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Key reference
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Title
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A ligand-Induced conformational change in the yersinia protein tyrosine phosphatase.
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Authors
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H.L.Schubert,
E.B.Fauman,
J.A.Stuckey,
J.E.Dixon,
M.A.Saper.
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Ref.
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Protein Sci, 1995,
4,
1904-1913.
[DOI no: ]
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PubMed id
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Note In the PDB file this reference is
annotated as "TO BE PUBLISHED".
The citation details given above were identified by an automated
search of PubMed on title and author
names, giving a
perfect match.
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Abstract
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Protein tyrosine phosphatases (PTPases) play critical roles in the intracellular
signal transduction pathways that regulate cell transformation, growth, and
proliferation. The structures of several different PTPases have revealed a
conserved active site architecture in which a phosphate-binding loop, together
with an invariant arginine, cradle the phosphate of a phosphotyrosine substrate
and poise it for nucleophilic attack by an invariant cysteine nucleophile. We
previously reported that binding of tungstate to the Yop51 PTPase from Yersinia
induced a loop conformational change that moved aspartic acid 356 into the
active site, where it can function as a general acid. This is consistent with
the aspartic acid donating a proton to the tyrosyl leaving group during the
initial hydrolysis step. In this report, using a similar structure of the
inactive Cys 403-->Ser mutant of the Yersinia PTPase complexed with sulfate,
we detail the structural and functional details of this conformational change.
In response to oxyanion binding, small perturbations occur in active site
residues, especially Arg 409, and trigger the loop to close. Interestingly, the
peptide bond following Asp 356 has flipped to ligate a buried, active site water
molecule that also hydrogen bonds to the bound sulfate anion and two invariant
glutamines. Loop closure also significantly decreases the solvent accessibility
of the bound oxyanion and could effectively shield catalytic intermediates from
phosphate acceptors other than water. We speculate that the intrinsic loop
flexibility of different PTPases may be related to their catalytic rate and may
play a role in the wide range of activities observed within this enzyme family.
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Figure 5.
Fig. 5. Conformationalchange in tpe WpDloopmoves
Asp 356 into active site and3.6 A romnoxgen of
the boundsulfate.The unbound structure (residues 354-
358) is shown in lueand the sulfate-bound structure is
shown in yellow with red oxygens and blue nitrogens. The
peptide ond between Asp 356 andGln 357 lips between
thetwo formingatype 11 fi-turn in theclosed
conformation with Gln 57 at the i + 2 position.Thefol-
lowing is a list of , shifts between the two forms: Trp 354,
1.9 A; Pro 355,3.8 ; Asp356, 5.0 A; Gln 357, 6.7 A;
Thr 358,4.4 A.
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Figure 7.
Fig. 7. A watermoleculetrapped in theac-
tive site f the sulfate-bound structure
bridgestheclosedWpD loop andthebound
oxyanion.The ater moleculeiswithin 3.3A
of severalresiduesincludingthe .sulfate.
istances from the waterare: 3.0 A to sul-
ateoxygen 04 thatis nalogous to thescis-
ileesterlinkage of phosphotyrosine,2.7 A
o sylfateoxygen 02,3.2 A Gln 446 OE 1,
.3 A o Gln450 Ne2, and 3.0br. to theam-
de of Gln 357 on pD loop. The car-
oxylsidechain of.Asp 356 A from
he ater and .6 A from 04.
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The above figures are
reprinted
from an Open Access publication published by the Protein Society:
Protein Sci
(1995,
4,
1904-1913)
copyright 1995.
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Secondary reference #1
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Title
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Dissecting the catalytic mechanism of protein-Tyrosine phosphatases.
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Authors
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Z.Y.Zhang,
Y.Wang,
J.E.Dixon.
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Ref.
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Proc Natl Acad Sci U S A, 1994,
91,
1624-1627.
[DOI no: ]
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PubMed id
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Secondary reference #2
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Title
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Crystal structure of yersinia protein tyrosine phosphatase at 2.5 a and the complex with tungstate.
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Authors
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J.A.Stuckey,
H.L.Schubert,
E.B.Fauman,
Z.Y.Zhang,
J.E.Dixon,
M.A.Saper.
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Ref.
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Nature, 1994,
370,
571-575.
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PubMed id
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Secondary reference #3
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Title
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Expression, Purification, And physicochemical characterization of a recombinant yersinia protein tyrosine phosphatase.
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Authors
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Z.Y.Zhang,
J.C.Clemens,
H.L.Schubert,
J.A.Stuckey,
M.W.Fischer,
D.M.Hume,
M.A.Saper,
J.E.Dixon.
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Ref.
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J Biol Chem, 1992,
267,
23759-23766.
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PubMed id
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