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PDBsum entry 2hnp
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Hydrolase(phosphorylation)
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PDB id
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2hnp
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Contents |
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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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O-phospho-L-tyrosyl-[protein] + H2O = L-tyrosyl-[protein] + phosphate
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O-phospho-L-tyrosyl-[protein]
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+
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H2O
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=
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L-tyrosyl-[protein]
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+
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phosphate
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Molecule diagrams generated from .mol files obtained from the
KEGG ftp site
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DOI no:
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Science
263:1397-1404
(1994)
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PubMed id:
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Crystal structure of human protein tyrosine phosphatase 1B.
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D.Barford,
A.J.Flint,
N.K.Tonks.
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ABSTRACT
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Protein tyrosine phosphatases (PTPs) constitute a family of receptor-like and
cytoplasmic signal transducing enzymes that catalyze the dephosphorylation of
phosphotyrosine residues and are characterized by homologous catalytic domains.
The crystal structure of a representative member of this family, the
37-kilodalton form (residues 1 to 321) of PTP1B, has been determined at 2.8 A
resolution. The enzyme consists of a single domain with the catalytic site
located at the base of a shallow cleft. The phosphate recognition site is
created from a loop that is located at the amino-terminus of an alpha helix.
This site is formed from an 11-residue sequence motif that is diagnostic of PTPs
and the dual specificity phosphatases, and that contains the catalytically
essential cysteine and arginine residues. The position of the invariant cysteine
residue within the phosphate binding site is consistent with its role as a
nucleophile in the catalytic reaction. The structure of PTP1B should serve as a
model for other members of the PTP family and as a framework for understanding
the mechanism of tyrosine dephosphorylation.
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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.Liu,
S.C.Kohout,
Q.Xu,
S.Müller,
C.R.Kimberlin,
E.Y.Isacoff,
and
D.L.Minor
(2012).
A glutamate switch controls voltage-sensitive phosphatase function.
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Nat Struct Mol Biol,
19,
633-641.
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PDB codes:
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A.Manford,
T.Xia,
A.K.Saxena,
C.Stefan,
F.Hu,
S.D.Emr,
and
Y.Mao
(2010).
Crystal structure of the yeast Sac1: implications for its phosphoinositide phosphatase function.
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EMBO J,
29,
1489-1498.
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PDB code:
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C.Brandsch,
T.Schmidt,
D.Behn,
K.Weisse,
A.S.Mueller,
and
G.I.Stangl
(2010).
Glutathione deficiency down-regulates hepatic lipogenesis in rats.
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Lipids Health Dis,
9,
50.
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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.M.Samet,
and
T.L.Tal
(2010).
Toxicological disruption of signaling homeostasis: tyrosine phosphatases as targets.
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Annu Rev Pharmacol Toxicol,
50,
215-235.
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J.P.Li,
Y.N.Fu,
Y.R.Chen,
and
T.H.Tan
(2010).
JNK pathway-associated phosphatase dephosphorylates focal adhesion kinase and suppresses cell migration.
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J Biol Chem,
285,
5472-5478.
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R.C.Edgar
(2010).
Quality measures for protein alignment benchmarks.
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Nucleic Acids Res,
38,
2145-2153.
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S.C.Yip,
S.Saha,
and
J.Chernoff
(2010).
PTP1B: a double agent in metabolism and oncogenesis.
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Trends Biochem Sci,
35,
442-449.
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S.Yalcin,
D.Marinkovic,
S.K.Mungamuri,
X.Zhang,
W.Tong,
R.Sellers,
and
S.Ghaffari
(2010).
ROS-mediated amplification of AKT/mTOR signalling pathway leads to myeloproliferative syndrome in Foxo3(-/-) mice.
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EMBO J,
29,
4118-4131.
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T.Scior,
J.A.Guevara-García,
F.J.Melendez,
H.H.Abdallah,
Q.T.Do,
and
P.Bernard
(2010).
Chimeric design, synthesis, and biological assays of a new nonpeptide insulin-mimetic vanadium compound to inhibit protein tyrosine phosphatase 1B.
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Drug Des Devel Ther,
4,
231-242.
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A.J.Barr,
E.Ugochukwu,
W.H.Lee,
O.N.King,
P.Filippakopoulos,
I.Alfano,
P.Savitsky,
N.A.Burgess-Brown,
S.Müller,
and
S.Knapp
(2009).
Large-scale structural analysis of the classical human protein tyrosine phosphatome.
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Cell,
136,
352-363.
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PDB codes:
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A.Trümpler,
B.Schlott,
P.Herrlich,
P.A.Greer,
and
F.D.Böhmer
(2009).
Calpain-mediated degradation of reversibly oxidized protein-tyrosine phosphatase 1B.
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FEBS J,
276,
5622-5633.
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D.Vidović,
and
S.C.Schürer
(2009).
Knowledge-based characterization of similarity relationships in the human protein-tyrosine phosphatase family for rational inhibitor design.
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J Med Chem,
52,
6649-6659.
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J.F.Wang,
K.Gong,
D.Q.Wei,
Y.X.Li,
and
K.C.Chou
(2009).
Molecular dynamics studies on the interactions of PTP1B with inhibitors: from the first phosphate-binding site to the second one.
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Protein Eng Des Sel,
22,
349-355.
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K.M.Doody,
A.Bourdeau,
and
M.L.Tremblay
(2009).
T-cell protein tyrosine phosphatase is a key regulator in immune cell signaling: lessons from the knockout mouse model and implications in human disease.
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Immunol Rev,
228,
325-341.
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M.L.Tremblay
(2009).
The PTP family photo album.
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Cell,
136,
213-214.
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M.S.Gentry,
J.E.Dixon,
and
C.A.Worby
(2009).
Lafora disease: insights into neurodegeneration from plant metabolism.
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Trends Biochem Sci,
34,
628-639.
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N.Brandes,
S.Schmitt,
and
U.Jakob
(2009).
Thiol-based redox switches in eukaryotic proteins.
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Antioxid Redox Signal,
11,
997.
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S.Hsu,
Y.Kim,
S.Li,
E.S.Durrant,
R.M.Pace,
V.L.Woods,
and
M.S.Gentry
(2009).
Structural insights into glucan phosphatase dynamics using amide hydrogen-deuterium exchange mass spectrometry.
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Biochemistry,
48,
9891-9902.
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T.A.Brandão,
H.Robinson,
S.J.Johnson,
and
A.C.Hengge
(2009).
Impaired acid catalysis by mutation of a protein loop hinge residue in a YopH mutant revealed by crystal structures.
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J Am Chem Soc,
131,
778-786.
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PDB codes:
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T.Scior,
H.G.Mack,
J.A.García,
and
W.Koch
(2009).
Antidiabetic Bis-Maltolato-OxoVanadium(IV): Conversion of inactive trans- to bioactive cis-BMOV for possible binding to target PTP-1B.
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Drug Des Devel Ther,
2,
221-231.
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A.M.Ibrahim,
and
Y.Kim
(2008).
Transient expression of protein tyrosine phosphatases encoded in Cotesia plutellae bracovirus inhibits insect cellular immune responses.
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Naturwissenschaften,
95,
25-32.
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B.Boivin,
S.Zhang,
J.L.Arbiser,
Z.Y.Zhang,
and
N.K.Tonks
(2008).
A modified cysteinyl-labeling assay reveals reversible oxidation of protein tyrosine phosphatases in angiomyolipoma cells.
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Proc Natl Acad Sci U S A,
105,
9959-9964.
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C.Madhurantakam,
V.R.Chavali,
and
A.K.Das
(2008).
Analyzing the catalytic mechanism of MPtpA: a low molecular weight protein tyrosine phosphatase from Mycobacterium tuberculosis through site-directed mutagenesis.
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Proteins,
71,
706-714.
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J.G.Zalatan,
T.D.Fenn,
and
D.Herschlag
(2008).
Comparative enzymology in the alkaline phosphatase superfamily to determine the catalytic role of an active-site metal ion.
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J Mol Biol,
384,
1174-1189.
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PDB code:
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K.Bharatham,
N.Bharatham,
Y.J.Kwon,
and
K.W.Lee
(2008).
Molecular dynamics simulation study of PTP1B with allosteric inhibitor and its application in receptor based pharmacophore modeling.
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J Comput Aided Mol Des,
22,
925-933.
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K.Lei,
D.M.Townsend,
and
K.D.Tew
(2008).
Protein cysteine sulfinic acid reductase (sulfiredoxin) as a regulator of cell proliferation and drug response.
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Oncogene,
27,
4877-4887.
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L.Tabernero,
A.R.Aricescu,
E.Y.Jones,
and
S.E.Szedlacsek
(2008).
Protein tyrosine phosphatases: structure-function relationships.
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FEBS J,
275,
867-882.
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M.Grunt,
V.Zárský,
and
F.Cvrcková
(2008).
Roots of angiosperm formins: the evolutionary history of plant FH2 domain-containing proteins.
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BMC Evol Biol,
8,
115.
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S.Liu,
L.F.Zeng,
L.Wu,
X.Yu,
T.Xue,
A.M.Gunawan,
Y.Q.Long,
and
Z.Y.Zhang
(2008).
Targeting inactive enzyme conformation: aryl diketoacid derivatives as a new class of PTP1B inhibitors.
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J Am Chem Soc,
130,
17075-17084.
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PDB codes:
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X.Y.Zhang,
V.L.Chen,
M.S.Rosen,
E.R.Blair,
A.M.Lone,
and
A.C.Bishop
(2008).
Allele-specific inhibition of divergent protein tyrosine phosphatases with a single small molecule.
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Bioorg Med Chem,
16,
8090-8097.
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A.A.Puhl,
R.J.Gruninger,
R.Greiner,
T.W.Janzen,
S.C.Mosimann,
and
L.B.Selinger
(2007).
Kinetic and structural analysis of a bacterial protein tyrosine phosphatase-like myo-inositol polyphosphatase.
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Protein Sci,
16,
1368-1378.
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PDB codes:
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B.A.Nakashima,
T.A.McAllister,
R.Sharma,
and
L.B.Selinger
(2007).
Diversity of phytases in the rumen.
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Microb Ecol,
53,
82-88.
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K.L.Jeffrey,
M.Camps,
C.Rommel,
and
C.R.Mackay
(2007).
Targeting dual-specificity phosphatases: manipulating MAP kinase signalling and immune responses.
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Nat Rev Drug Discov,
6,
391-403.
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L.I.Pao,
K.Badour,
K.A.Siminovitch,
and
B.G.Neel
(2007).
Nonreceptor protein-tyrosine phosphatases in immune cell signaling.
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Annu Rev Immunol,
25,
473-523.
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L.Yu,
U.Kelly,
J.N.Ebright,
G.Malek,
P.Saloupis,
D.W.Rickman,
B.S.McKay,
V.Y.Arshavsky,
and
C.Bowes Rickman
(2007).
Oxidative stress-induced expression and modulation of Phosphatase of Regenerating Liver-1 (PRL-1) in mammalian retina.
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Biochim Biophys Acta,
1773,
1473-1482.
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S.J.Kim,
D.G.Jeong,
T.S.Yoon,
J.H.Son,
S.K.Cho,
S.E.Ryu,
and
J.H.Kim
(2007).
Crystal structure of human TMDP, a testis-specific dual specificity protein phosphatase: implications for substrate specificity.
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Proteins,
66,
239-245.
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PDB code:
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T.S.Girish,
and
B.Gopal
(2007).
The crystal structure of the catalytic domain of the chick retinal neurite inhibitor-receptor protein tyrosine phosphatase CRYP-2/cPTPRO.
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Proteins,
68,
1011-1015.
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PDB code:
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A.J.Barr,
J.E.Debreczeni,
J.Eswaran,
and
S.Knapp
(2006).
Crystal structure of human protein tyrosine phosphatase 14 (PTPN14) at 1.65-A resolution.
|
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Proteins,
63,
1132-1136.
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PDB code:
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A.J.Barr,
and
S.Knapp
(2006).
MAPK-specific tyrosine phosphatases: new targets for drug discovery?
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Trends Pharmacol Sci,
27,
525-530.
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G.X.Liu,
J.Z.Tan,
C.Y.Niu,
J.H.Shen,
X.M.Luo,
X.Shen,
K.X.Chen,
and
H.L.Jiang
(2006).
Molecular dynamics simulations of interaction between protein-tyrosine phosphatase 1B and a bidentate inhibitor.
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Acta Pharmacol Sin,
27,
100-110.
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J.Eswaran,
J.E.Debreczeni,
E.Longman,
A.J.Barr,
and
S.Knapp
(2006).
The crystal structure of human receptor protein tyrosine phosphatase kappa phosphatase domain 1.
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Protein Sci,
15,
1500-1505.
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PDB codes:
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A.Salmeen,
and
D.Barford
(2005).
Functions and mechanisms of redox regulation of cysteine-based phosphatases.
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Antioxid Redox Signal,
7,
560-577.
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C.Grundner,
H.L.Ng,
and
T.Alber
(2005).
Mycobacterium tuberculosis protein tyrosine phosphatase PtpB structure reveals a diverged fold and a buried active site.
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Structure,
13,
1625-1634.
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PDB code:
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C.Madhurantakam,
E.Rajakumara,
P.A.Mazumdar,
B.Saha,
D.Mitra,
H.G.Wiker,
R.Sankaranarayanan,
and
A.K.Das
(2005).
Crystal structure of low-molecular-weight protein tyrosine phosphatase from Mycobacterium tuberculosis at 1.9-A resolution.
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J Bacteriol,
187,
2175-2181.
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PDB codes:
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H.J.Nam,
F.Poy,
H.Saito,
and
C.A.Frederick
(2005).
Structural basis for the function and regulation of the receptor protein tyrosine phosphatase CD45.
|
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J Exp Med,
201,
441-452.
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PDB codes:
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I.Gouni-Berthold,
E.Giannakidou,
D.Müller-Wieland,
M.Faust,
J.Kotzka,
H.K.Berthold,
and
W.Krone
(2005).
The Pro387Leu variant of protein tyrosine phosphatase-1B is not associated with diabetes mellitus type 2 in a German population.
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J Intern Med,
257,
272-280.
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K.Hamada,
M.Kato,
T.Shimizu,
K.Ihara,
T.Mizuno,
and
T.Hakoshima
(2005).
Crystal structure of the protein histidine phosphatase SixA in the multistep His-Asp phosphorelay.
|
| |
Genes Cells,
10,
1.
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PDB codes:
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L.Bialy,
and
H.Waldmann
(2005).
Inhibitors of protein tyrosine phosphatases: next-generation drugs?
|
| |
Angew Chem Int Ed Engl,
44,
3814-3839.
|
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R.G.Coleman,
M.A.Burr,
D.L.Souvaine,
and
A.C.Cheng
(2005).
An intuitive approach to measuring protein surface curvature.
|
| |
Proteins,
61,
1068-1074.
|
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S.Li,
R.S.Depetris,
D.Barford,
J.Chernoff,
and
S.R.Hubbard
(2005).
Crystal structure of a complex between protein tyrosine phosphatase 1B and the insulin receptor tyrosine kinase.
|
| |
Structure,
13,
1643-1651.
|
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PDB code:
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A.K.Pedersen,
G.H.Peters G,
K.B.Møller,
L.F.Iversen,
and
J.S.Kastrup
(2004).
Water-molecule network and active-site flexibility of apo protein tyrosine phosphatase 1B.
|
| |
Acta Crystallogr D Biol Crystallogr,
60,
1527-1534.
|
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PDB code:
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B.Provost,
P.Varricchio,
E.Arana,
E.Espagne,
P.Falabella,
E.Huguet,
R.La Scaleia,
L.Cattolico,
M.Poirié,
C.Malva,
J.A.Olszewski,
F.Pennacchio,
and
J.M.Drezen
(2004).
Bracoviruses contain a large multigene family coding for protein tyrosine phosphatases.
|
| |
J Virol,
78,
13090-13103.
|
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|
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C.Wiesmann,
K.J.Barr,
J.Kung,
J.Zhu,
D.A.Erlanson,
W.Shen,
B.J.Fahr,
M.Zhong,
L.Taylor,
M.Randal,
R.S.McDowell,
and
S.K.Hansen
(2004).
Allosteric inhibition of protein tyrosine phosphatase 1B.
|
| |
Nat Struct Mol Biol,
11,
730-737.
|
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PDB codes:
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F.Cvrcková,
M.Novotný,
D.Pícková,
and
V.Zárský
(2004).
Formin homology 2 domains occur in multiple contexts in angiosperms.
|
| |
BMC Genomics,
5,
44.
|
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S.D.Taylor,
and
B.Hill
(2004).
Recent advances in protein tyrosine phosphatase 1B inhibitors.
|
| |
Expert Opin Investig Drugs,
13,
199-214.
|
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|
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A.M.Ah Fong,
and
H.S.Judelson
(2003).
Cell cycle regulator Cdc14 is expressed during sporulation but not hyphal growth in the fungus-like oomycete Phytophthora infestans.
|
| |
Mol Microbiol,
50,
487-494.
|
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|
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A.Salmeen,
J.N.Andersen,
M.P.Myers,
T.C.Meng,
J.A.Hinks,
N.K.Tonks,
and
D.Barford
(2003).
Redox regulation of protein tyrosine phosphatase 1B involves a sulphenyl-amide intermediate.
|
| |
Nature,
423,
769-773.
|
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PDB codes:
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 |
M.Bearzatto,
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PDB code:
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D.T.Haynie,
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The N-terminal domains of tensin and auxilin are phosphatase homologues.
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Protein Sci,
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Identification of an essential acidic residue in Cdc25 protein phosphatase and a general three-dimensional model for a core region in protein phosphatases.
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Protein Sci,
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EMBO J,
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Probing the function of Asp128 in the lower molecular weight protein-tyrosine phosphatase-catalyzed reaction. A pre-steady-state and steady-state kinetic investigation.
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Biochemistry,
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S.G.Grdadolnik,
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A.Buhr,
and
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(1996).
Solution structure of the IIB domain of the glucose transporter of Escherichia coli.
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Biochemistry,
35,
11286-11292.
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PDB code:
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M.Gamper,
P.K.Howard,
T.Hunter,
and
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Multiple roles of the novel protein tyrosine phosphatase PTP3 during Dictyostelium growth and development.
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Mol Cell Biol,
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Small molecule interactions with protein-tyrosine phosphatase PTP1B and their use in inhibitor design.
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Biochemistry,
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Reactivity of alcohols toward the phosphoenzyme intermediate in the protein-tyrosine phosphatase-catalyzed reaction: probing the transition state of the dephosphorylation step.
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Biochemistry,
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Mol Cell Biochem,
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Crystallization and preliminary crystallographic study of human CksHs1: a cell cycle regulatory protein.
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Proteins,
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Mol Cell Biochem,
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D.Barford,
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Nat Struct Biol,
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Curr Opin Struct Biol,
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D.McNamara,
E.M.Dobrusin,
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Differentiation of peptide molecular recognition by phospholipase C gamma-1 Src homology-2 domain and a mutant Tyr phosphatase PTP1bC215S.
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Protein Sci,
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D.Peters,
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Lactose-specific enzyme II of the phosphoenolpyruvate-dependent phosphotransferase system of Staphylococcus aureus. Purification of the histidine-tagged transmembrane component IICBLac and its hydrophilic IIB domain by metal-affinity chromatography, and functional characterization.
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Eur J Biochem,
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A ligand-induced conformational change in the Yersinia protein tyrosine phosphatase.
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Protein Sci,
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PDB code:
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H.R.Matthews
(1995).
Protein kinases and phosphatases that act on histidine, lysine, or arginine residues in eukaryotic proteins: a possible regulator of the mitogen-activated protein kinase cascade.
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Structure and catalytic properties of protein tyrosine phosphatases.
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Ann N Y Acad Sci,
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A catalytic mechanism for the dual-specific phosphatases.
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Proc Natl Acad Sci U S A,
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Preliminary crystallization studies of calmodulin-dependent protein phosphatase (calcineurin) from bovine brain.
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Mol Cell Biochem,
149,
127-130.
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N.Perrimon,
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Dissection of the Torso signal transduction pathway in Drosophila.
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Mol Reprod Dev,
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C.D.Schaub,
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Phosphotyrosine-dependent interaction of SHC and insulin receptor substrate 1 with the NPEY motif of the insulin receptor via a novel non-SH2 domain.
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Mol Cell Biol,
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2500-2508.
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T.F.Jenny,
D.L.Gerloff,
M.A.Cohen,
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Predicted secondary and supersecondary structure for the serine-threonine-specific protein phosphatase family.
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Y.Li,
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Properties of a baculovirus mutant defective in the protein phosphatase gene.
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J Virol,
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Recognition and specificity in protein tyrosine kinase-mediated signalling.
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S.E.Shoelson,
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J.Kuriyan
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Crystal structures of peptide complexes of the amino-terminal SH2 domain of the Syp tyrosine phosphatase.
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Structure,
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|
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PDB codes:
|
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|
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E.Hoppe,
P.F.Berne,
D.Stock,
J.S.Rasmussen,
N.P.Møller,
A.Ullrich,
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Expression, purification and crystallization of human phosphotyrosine phosphatase 1B.
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Eur J Biochem,
223,
1069-1077.
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G.Hannig,
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R.L.Erikson
(1994).
Negative regulation of mitosis in fission yeast by catalytically inactive pyp1 and pyp2 mutants.
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Proc Natl Acad Sci U S A,
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10084-10088.
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H.Yu,
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S.L.Schreiber
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Signalling an interest.
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Nat Struct Biol,
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|
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J.Wagner,
D.Boerboom,
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M.L.Tremblay
(1994).
Molecular cloning and tissue-specific RNA processing of a murine receptor-type protein tyrosine phosphatase.
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Eur J Biochem,
226,
773-782.
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|
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P.R.Clarke
(1994).
Signal transduction. Switching off MAP kinases.
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Curr Biol,
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T.Furukawa,
M.Itoh,
N.X.Krueger,
M.Streuli,
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H.Saito
(1994).
Specific interaction of the CD45 protein-tyrosine phosphatase with tyrosine-phosphorylated CD3 zeta chain.
|
| |
Proc Natl Acad Sci U S A,
91,
10928-10932.
|
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|
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T.Noguchi,
T.Matozaki,
K.Horita,
Y.Fujioka,
and
M.Kasuga
(1994).
Role of SH-PTP2, a protein-tyrosine phosphatase with Src homology 2 domains, in insulin-stimulated Ras activation.
|
| |
Mol Cell Biol,
14,
6674-6682.
|
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|
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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
codes are
shown on the right.
|
');
}
}
 |