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PDBsum entry 2azr
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Contents |
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* Residue conservation analysis
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PDB id:
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Hydrolase
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Title:
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Crystal structure of ptp1b with bicyclic thiophene inhibitor
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Structure:
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Tyrosine-protein phosphatase, non-receptor type 1. Chain: a. Fragment: catalytic domain, residues 1-299. Synonym: protein-tyrosine phosphatase 1b, ptp-1b. Engineered: yes
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Source:
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Homo sapiens. Human. Organism_taxid: 9606. Gene: ptpn1, ptp1b. Expressed in: escherichia coli bl21. Expression_system_taxid: 511693.
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Resolution:
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2.00Å
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R-factor:
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0.223
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R-free:
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0.250
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Authors:
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A.F.Moretto,S.J.Kirincich,W.X.Xu,M.J.Smith,Z.K.Wan,D.P.Wilson, B.C.Follows,E.Binnun,D.Joseph-Mccarthy,K.Foreman,D.V.Erbe,Y.L.Zhang, S.K.Tam,S.Y.Tam,J.Lee
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Key ref:
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A.F.Moretto
et al.
(2006).
Bicyclic and tricyclic thiophenes as protein tyrosine phosphatase 1B inhibitors.
Bioorg Med Chem Lett,
14,
2162-2177.
PubMed id:
DOI:
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Date:
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12-Sep-05
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Release date:
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06-Dec-05
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PROCHECK
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Headers
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References
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P18031
(PTN1_HUMAN) -
Tyrosine-protein phosphatase non-receptor type 1 from Homo sapiens
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Seq:
Struc:
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435 a.a.
297 a.a.
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Key: |
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PfamA domain |
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Secondary structure |
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CATH domain |
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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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Bioorg Med Chem Lett
14:2162-2177
(2006)
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PubMed id:
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Bicyclic and tricyclic thiophenes as protein tyrosine phosphatase 1B inhibitors.
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A.F.Moretto,
S.J.Kirincich,
W.X.Xu,
M.J.Smith,
Z.K.Wan,
D.P.Wilson,
B.C.Follows,
E.Binnun,
D.Joseph-McCarthy,
K.Foreman,
D.V.Erbe,
Y.L.Zhang,
S.K.Tam,
S.Y.Tam,
J.Lee.
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ABSTRACT
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A novel pyridothiophene inhibitor of PTP1B was discovered by rational screening
of phosphotyrosine mimics at high micromolar concentrations. The potency of this
lead compound has been improved significantly by medicinal chemistry guided by
X-ray crystallography and molecular modeling. Excellent consistency has been
observed between structure-activity relationships and structural information
from PTP1B-inhibitor complexes.
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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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J.P.Yesudas,
F.B.Sayyed,
and
C.H.Suresh
(2011).
Analysis of structural water and CH···π interactions in HIV-1 protease and PTP1B complexes using a hydrogen bond prediction tool, HBPredicT.
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J Mol Model,
17,
401-413.
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C.Lô,
J.J.Aaron,
V.Kozmík,
J.Svoboda,
J.C.Brochon,
and
L.Na
(2010).
Synthesis, electrochemical, and optical properties of new fluorescent, substituted thieno[3,2-b][1]benzothiophenes.
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J Fluoresc,
20,
1037-1047.
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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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M.L.Mohler,
Y.He,
Z.Wu,
D.J.Hwang,
and
D.D.Miller
(2009).
Recent and emerging anti-diabetes targets.
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Med Res Rev,
29,
125-195.
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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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R.Maccari,
P.Paoli,
R.Ottanà,
M.Jacomelli,
R.Ciurleo,
G.Manao,
T.Steindl,
T.Langer,
M.G.Vigorita,
and
G.Camici
(2007).
5-Arylidene-2,4-thiazolidinediones as inhibitors of protein tyrosine phosphatases.
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Bioorg Med Chem,
15,
5137-5149.
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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
