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PDBsum entry 4py1
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PDB id:
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Transferase
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Title:
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Crystal structure of tyk2 in complex with compound 15, 6-((2,5- dimethoxyphenyl)thio)-3-(1-methyl-1h-pyrazol-4-yl)-[1,2,4]triazolo[4, 3-b]pyridazine
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Structure:
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Non-receptor tyrosine-protein kinase tyk2. Chain: a. Engineered: yes. Mutation: yes
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Source:
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Homo sapiens. Human. Organism_taxid: 9606. Gene: tyk2. Expressed in: escherichia coli. Expression_system_taxid: 562
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Resolution:
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2.16Å
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R-factor:
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0.184
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R-free:
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0.236
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Authors:
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S.Han,J.D.Knafels
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Key ref:
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P.Galatsis
et al.
(2014).
Kinase domain inhibition of leucine rich repeat kinase 2 (LRRK2) using a [1,2,4]triazolo[4,3-b]pyridazine scaffold.
Bioorg Med Chem Lett,
24,
4132-4140.
PubMed id:
DOI:
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Date:
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25-Mar-14
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Release date:
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03-Sep-14
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PROCHECK
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Headers
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References
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P29597
(TYK2_HUMAN) -
Non-receptor tyrosine-protein kinase TYK2 from Homo sapiens
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Seq:
Struc:
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1187 a.a.
290 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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*
PDB and UniProt seqs differ
at 6 residue positions (black
crosses)
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Enzyme class:
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E.C.2.7.10.2
- non-specific 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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Bioorg Med Chem Lett
24:4132-4140
(2014)
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PubMed id:
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Kinase domain inhibition of leucine rich repeat kinase 2 (LRRK2) using a [1,2,4]triazolo[4,3-b]pyridazine scaffold.
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P.Galatsis,
J.L.Henderson,
B.L.Kormos,
S.Han,
R.G.Kurumbail,
T.T.Wager,
P.R.Verhoest,
G.S.Noell,
Y.Chen,
E.Needle,
Z.Berger,
S.J.Steyn,
C.Houle,
W.D.Hirst.
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ABSTRACT
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Leucine rich repeat kinase 2 (LRRK2) has been genetically linked to Parkinson's
disease (PD). The most common mutant, G2019S, increases kinase activity, thus
LRRK2 kinase inhibitors are potentially useful in the treatment of PD. We herein
disclose the structure, potential ligand-protein binding interactions, and
pharmacological profiling of potent and highly selective kinase inhibitors based
on a triazolopyridazine chemical scaffold.
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Links
