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PDBsum entry 3lw0
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Contents |
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* Residue conservation analysis
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PDB id:
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Transferase
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Title:
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Igf-1rk in complex with ligand msc1609119a-1
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Structure:
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Insulin-like growth factor 1 receptor. Chain: a, b, c, d. Fragment: protein kinase, unp residues 983-1286. Synonym: igf-1 receptor kinase, insulin-like growth factor i receptor, igf-i receptor, insulin-like growth factor 1 receptor alpha chain, insulin-like growth factor 1 receptor beta chain. Engineered: yes. Mutation: yes
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Source:
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Homo sapiens. Human. Organism_taxid: 9606. Gene: igf1r. Expressed in: spodoptera frugiperda. Expression_system_taxid: 7108
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Resolution:
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1.79Å
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R-factor:
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0.157
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R-free:
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0.185
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Authors:
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U.Graedler,T.Heinrich,H.Boettcher,A.Blaukat,A.Shutes,B.Askew
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Key ref:
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T.Heinrich
et al.
(2010).
Allosteric IGF-1R Inhibitors.
ACS Med Chem Lett,
1,
199-203.
PubMed id:
DOI:
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Date:
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23-Feb-10
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Release date:
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29-Sep-10
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PROCHECK
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Headers
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References
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P08069
(IGF1R_HUMAN) -
Insulin-like growth factor 1 receptor from Homo sapiens
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Seq:
Struc:
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1367 a.a.
292 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.2.7.10.1
- receptor protein-tyrosine kinase.
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Reaction:
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L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H+
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L-tyrosyl-[protein]
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+
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ATP
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=
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O-phospho-L-tyrosyl-[protein]
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+
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ADP
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+
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H(+)
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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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ACS Med Chem Lett
1:199-203
(2010)
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PubMed id:
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Allosteric IGF-1R Inhibitors.
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T.Heinrich,
U.Grädler,
H.Böttcher,
A.Blaukat,
A.Shutes.
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ABSTRACT
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Targeting allosteric protein sites is a promising approach to interfere
selectively with cellular signaling cascades. We have discovered a novel class
of allosteric insulin-like growth factor-I receptor (IGF-1R) inhibitors.
3-Cyano-1H-indole-7-carboxylic acid
{1-[4-(5-cyano-1H-indol-3-yl)butyl]piperidin-4-yl}amide (10) was found with
nanomolar biochemical, micromolar, cellular IGF-1R activity and no relevant
interference with cellular insulin receptor signaling up to 30 μM. The
allosteric binding site was characterized by X-ray crystallographic studies, and
the structural information was used to explain the unique mode of action of this
new class of inhibitors.
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Links
