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PDBsum entry 1bzc
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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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Biochemistry
37:17773-17783
(1998)
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PubMed id:
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Structural basis for inhibition of the protein tyrosine phosphatase 1B by phosphotyrosine peptide mimetics.
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M.R.Groves,
Z.J.Yao,
P.P.Roller,
T.R.Burke,
D.Barford.
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ABSTRACT
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Protein tyrosine phosphatases regulate diverse cellular processes and represent
important targets for therapeutic intervention in a number of diseases. The
crystal structures of protein tyrosine phosphatase 1B (PTP1B) in complex with
small molecule inhibitors based upon two classes of phosphotyrosine mimetics,
the (difluoronaphthylmethyl)phosphonic acids and the fluoromalonyl tyrosines,
have been determined to resolutions greater than 2.3 A. The fluoromalonyl
tyrosine residue was incorporated within a cyclic hexapeptide modeled on an
autophosphorylation site of the epidermal growth factor receptor. The structure
of this inhibitor bound to PTP1B represents the first crystal structure of a
non-phosphonate-containing inhibitor and reveals the mechanism of
phosphotyrosine mimicry by the fluoromalonyl tyrosine residue and the nature of
its interactions within the catalytic site of PTP1B. In contrast to complexes of
PTP1B with phosphotyrosine-containing peptides, binding of the fluoromalonyl
tyrosine residue to the catalytic site of PTP1B is not accompanied by closure of
the catalytic site WPD loop. Structures of PTP1B in complex with the
(difluoronaphthylmethyl)phosphonic acid derivatives reveal that substitutions of
the naphthalene ring modulate the mode of inhibitor binding to the catalytic
site and provide the potential for enhanced inhibitor affinity and the
generation of PTP-specific inhibitors. These results provide a framework for the
rational design of higher affinity and more specific phosphotyrosine mimetic
inhibitors of not only protein tyrosine phosphatases but also SH2 and PTB
domains.
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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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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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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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S.A.Allman,
H.H.Jensen,
B.Vijayakrishnan,
J.A.Garnett,
E.Leon,
Y.Liu,
D.C.Anthony,
N.R.Sibson,
T.Feizi,
S.Matthews,
and
B.G.Davis
(2009).
Potent fluoro-oligosaccharide probes of adhesion in Toxoplasmosis.
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Chembiochem,
10,
2522-2529.
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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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Y.Ishino,
C.Zhu,
D.L.Harris,
and
N.C.Joyce
(2008).
Protein tyrosine phosphatase-1B (PTP1B) helps regulate EGF-induced stimulation of S-phase entry in human corneal endothelial cells.
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Mol Vis,
14,
61-70.
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J.Xie,
and
C.T.Seto
(2007).
A two stage click-based library of protein tyrosine phosphatase inhibitors.
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Bioorg Med Chem,
15,
458-473.
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K.M.Picha,
S.S.Patel,
S.Mandiyan,
J.Koehn,
and
L.P.Wennogle
(2007).
The role of the C-terminal domain of protein tyrosine phosphatase-1B in phosphatase activity and substrate binding.
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J Biol Chem,
282,
2911-2917.
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U.Schieborr,
M.Vogtherr,
B.Elshorst,
M.Betz,
S.Grimme,
B.Pescatore,
T.Langer,
K.Saxena,
and
H.Schwalbe
(2005).
How much NMR data is required to determine a protein-ligand complex structure?
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Chembiochem,
6,
1891-1898.
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W.H.Lee,
A.Raas-Rotschild,
M.A.Miteva,
G.Bolasco,
A.Rein,
D.Gillis,
D.Vidaud,
M.Vidaud,
B.O.Villoutreix,
and
B.Parfait
(2005).
Noonan syndrome type I with PTPN11 3 bp deletion: structure-function implications.
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Proteins,
58,
7.
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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.
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Acta Crystallogr D Biol Crystallogr,
60,
1527-1534.
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PDB code:
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I.K.Lund,
H.S.Andersen,
L.F.Iversen,
O.H.Olsen,
K.B.Møller,
A.K.Pedersen,
Y.Ge,
D.D.Holsworth,
M.J.Newman,
F.U.Axe,
and
N.P.Møller
(2004).
Structure-based design of selective and potent inhibitors of protein-tyrosine phosphatase beta.
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J Biol Chem,
279,
24226-24235.
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J.A.Olsen,
D.W.Banner,
P.Seiler,
B.Wagner,
T.Tschopp,
U.Obst-Sander,
M.Kansy,
K.Müller,
and
F.Diederich
(2004).
Fluorine interactions at the thrombin active site: protein backbone fragments H-C(alpha)-C=O comprise a favorable C-F environment and interactions of C-F with electrophiles.
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Chembiochem,
5,
666-675.
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A.Nayeem,
S.Krystek,
and
T.Stouch
(2003).
An assessment of protein-ligand binding site polarizability.
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Biopolymers,
70,
201-211.
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J.P.Sun,
A.A.Fedorov,
S.Y.Lee,
X.L.Guo,
K.Shen,
D.S.Lawrence,
S.C.Almo,
and
Z.Y.Zhang
(2003).
Crystal structure of PTP1B complexed with a potent and selective bidentate inhibitor.
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J Biol Chem,
278,
12406-12414.
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PDB codes:
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L.F.Iversen,
K.B.Moller,
A.K.Pedersen,
G.H.Peters,
A.S.Petersen,
H.S.Andersen,
S.Branner,
S.B.Mortensen,
and
N.P.Moller
(2002).
Structure determination of T cell protein-tyrosine phosphatase.
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J Biol Chem,
277,
19982-19990.
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PDB code:
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T.O.Johnson,
J.Ermolieff,
and
M.R.Jirousek
(2002).
Protein tyrosine phosphatase 1B inhibitors for diabetes.
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Nat Rev Drug Discov,
1,
696-709.
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G.Scapin,
S.Patel,
V.Patel,
B.Kennedy,
and
E.Asante-Appiah
(2001).
The structure of apo protein-tyrosine phosphatase 1B C215S mutant: more than just an S --> O change.
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Protein Sci,
10,
1596-1605.
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PDB code:
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Y.T.Chen,
M.B.Onaran,
C.J.Doss,
and
C.T.Seto
(2001).
alpha-Ketocarboxylic acid-based inhibitors of protein tyrosine phosphatases.
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Bioorg Med Chem Lett,
11,
1935-1938.
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H.S.Andersen,
L.F.Iversen,
C.B.Jeppesen,
S.Branner,
K.Norris,
H.B.Rasmussen,
K.B.Møller,
and
N.P.Møller
(2000).
2-(oxalylamino)-benzoic acid is a general, competitive inhibitor of protein-tyrosine phosphatases.
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J Biol Chem,
275,
7101-7108.
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PDB codes:
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L.F.Iversen,
H.S.Andersen,
S.Branner,
S.B.Mortensen,
G.H.Peters,
K.Norris,
O.H.Olsen,
C.B.Jeppesen,
B.F.Lundt,
W.Ripka,
K.B.Møller,
and
N.P.Møller
(2000).
Structure-based design of a low molecular weight, nonphosphorus, nonpeptide, and highly selective inhibitor of protein-tyrosine phosphatase 1B.
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J Biol Chem,
275,
10300-10307.
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PDB codes:
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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.
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Links
