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PDBsum entry 1xbo
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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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Ptp1b complexed with isoxazole carboxylic acid
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Structure:
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Protein-tyrosine phosphatase, non-receptor type 1. Chain: a. Fragment: ptp1b catalytic domain. 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. Expression_system_taxid: 562.
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Resolution:
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2.50Å
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R-factor:
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0.211
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R-free:
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0.219
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Authors:
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H.Zhao,G.Liu,Z.Xin,M.Serby,Z.Pei,B.G.Szczepankiewicz,P.J.Hajduk, C.Abad-Zapatero,C.W.Hutchins,T.H.Lubben,S.J.Ballaron,D.L.Hassach, W.Kaszubska,C.M.Rondinone,J.M.Trevillyan,M.R.Jirousek
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Key ref:
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H.Zhao
et al.
(2004).
Isoxazole carboxylic acids as protein tyrosine phosphatase 1B (PTP1B) inhibitors.
Bioorg Med Chem Lett,
14,
5543-5546.
PubMed id:
DOI:
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Date:
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31-Aug-04
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Release date:
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19-Oct-04
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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.
299 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
14:5543-5546
(2004)
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PubMed id:
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Isoxazole carboxylic acids as protein tyrosine phosphatase 1B (PTP1B) inhibitors.
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H.Zhao,
G.Liu,
Z.Xin,
M.D.Serby,
Z.Pei,
B.G.Szczepankiewicz,
P.J.Hajduk,
C.Abad-Zapatero,
C.W.Hutchins,
T.H.Lubben,
S.J.Ballaron,
D.L.Haasch,
W.Kaszubska,
C.M.Rondinone,
J.M.Trevillyan,
M.R.Jirousek.
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ABSTRACT
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Guided by X-ray crystallography, we have extended the structure-activity
relationship (SAR) study on an isoxazole carboxylic acid-based PTP1B inhibitor
(1) and more potent and equally selective (>20-fold selectivity over the
highly homologous T-cell PTPase, TCPTP) PTP1B inhibitors were identified.
Inhibitor 7 demonstrated good cellular activity against PTP1B in COS 7 cells.
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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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F.Liu,
R.M.Hakami,
B.Dyas,
M.Bahta,
G.T.Lountos,
D.S.Waugh,
R.G.Ulrich,
and
T.R.Burke
(2010).
A rapid oxime linker-based library approach to identification of bivalent inhibitors of the Yersinia pestis protein-tyrosine phosphatase, YopH.
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Bioorg Med Chem Lett,
20,
2813-2816.
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N.J.Beresford,
D.Mulhearn,
B.Szczepankiewicz,
G.Liu,
M.E.Johnson,
A.Fordham-Skelton,
C.Abad-Zapatero,
J.S.Cavet,
and
L.Tabernero
(2009).
Inhibition of MptpB phosphatase from Mycobacterium tuberculosis impairs mycobacterial survival in macrophages.
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J Antimicrob Chemother,
63,
928-936.
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R.Maccari,
R.Ottanà,
R.Ciurleo,
P.Paoli,
G.Manao,
G.Camici,
C.Laggner,
and
T.Langer
(2009).
Structure-based optimization of benzoic acids as inhibitors of protein tyrosine phosphatase 1B and low molecular weight protein tyrosine phosphatase.
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ChemMedChem,
4,
957-962.
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H.Zhao
(2007).
Scaffold selection and scaffold hopping in lead generation: a medicinal chemistry perspective.
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Drug Discov Today,
12,
149-155.
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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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S.Lee,
and
Q.Wang
(2007).
Recent development of small molecular specific inhibitor of protein tyrosine phosphatase 1B.
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Med Res Rev,
27,
553-573.
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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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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.
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Links
