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PDBsum entry 5oy4
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PDB id:
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Transferase
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Title:
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Gsk3beta complex with n-(6-(3,4-dihydroxyphenyl)-1h-pyrazolo[3,4- b]pyridin-3-yl)acetamide
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Structure:
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Glycogen synthase kinase-3 beta. Chain: a, b. Synonym: gsk-3 beta,serine/threonine-protein kinase gsk3b. Engineered: yes. Proto-oncogene frat1. Chain: x, y. Synonym: frequently rearranged in advanced t-cell lymphomas 1,frat-1. Engineered: yes
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Source:
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Homo sapiens. Human. Organism_taxid: 9606. Gene: gsk3b. Expressed in: spodoptera frugiperda. Expression_system_taxid: 7108. Synthetic: yes. Organism_taxid: 9606
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Resolution:
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3.20Å
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R-factor:
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0.196
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R-free:
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0.229
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Authors:
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B.D.Bax,M.A.Convery
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Key ref:
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Z.A.Henley
et al.
(2017).
From PIM1 to PI3Kδ via GSK3β: Target Hopping through the Kinome.
ACS Med Chem Lett,
8,
1093-1098.
PubMed id:
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Date:
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07-Sep-17
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Release date:
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01-Nov-17
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PROCHECK
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Headers
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References
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P49841
(GSK3B_HUMAN) -
Glycogen synthase kinase-3 beta from Homo sapiens
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Seq:
Struc:
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420 a.a.
350 a.a.
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Enzyme class 1:
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Chains A, B:
E.C.2.7.11.1
- non-specific serine/threonine protein kinase.
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Reaction:
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1.
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L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP + H+
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2.
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L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] + ADP + H+
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L-seryl-[protein]
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+
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ATP
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=
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O-phospho-L-seryl-[protein]
Bound ligand (Het Group name = )
matches with 45.45% similarity
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+
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ADP
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+
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H(+)
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L-threonyl-[protein]
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+
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ATP
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=
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O-phospho-L-threonyl-[protein]
Bound ligand (Het Group name = )
matches with 45.45% similarity
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+
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ADP
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+
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H(+)
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Enzyme class 2:
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Chains A, B:
E.C.2.7.11.26
- [tau protein] kinase.
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Reaction:
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1.
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L-seryl-[tau protein] + ATP = O-phospho-L-seryl-[tau protein] + ADP + H+
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2.
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L-threonyl-[tau protein] + ATP = O-phospho-L-threonyl-[tau protein] + ADP + H+
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L-seryl-[tau protein]
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+
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ATP
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=
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O-phospho-L-seryl-[tau protein]
Bound ligand (Het Group name = )
matches with 45.45% similarity
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+
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ADP
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+
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H(+)
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L-threonyl-[tau protein]
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+
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ATP
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=
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O-phospho-L-threonyl-[tau protein]
Bound ligand (Het Group name = )
matches with 45.45% similarity
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+
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ADP
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+
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H(+)
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Note, where more than one E.C. class is given (as above), each may
correspond to a different protein domain or, in the case of polyprotein
precursors, to a different mature protein.
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Molecule diagrams generated from .mol files obtained from the
KEGG ftp site
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ACS Med Chem Lett
8:1093-1098
(2017)
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PubMed id:
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From PIM1 to PI3Kδ via GSK3β: Target Hopping through the Kinome.
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Z.A.Henley,
B.D.Bax,
L.M.Inglesby,
A.Champigny,
S.Gaines,
P.Faulder,
J.Le,
D.A.Thomas,
Y.Washio,
I.R.Baldwin.
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ABSTRACT
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Selective inhibitors of phosphoinositide 3-kinase delta are of interest for the
treatment of inflammatory diseases. Initial optimization of a 3-substituted
indazole hit compound targeting the kinase PIM1 focused on improving selectivity
over GSK3β through consideration of differences in the ATP binding pockets.
Continued kinase cross-screening showed PI3Kδ activity in a series of
4,6-disubstituted indazole compounds, and subsequent structure-activity
relationship exploration led to the discovery of an indole-containing lead
compound as a potent PI3Kδ inhibitor with selectivity over the other PI3K
isoforms.
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