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PDBsum entry 4idt
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Transferase/transferase inhibitor
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PDB id
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4idt
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PDB id:
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| Name: |
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Transferase/transferase inhibitor
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Title:
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Crystal structure of nik with 11-bromo-5,6,7,8-tetrahydropyrimido[4', 5':3,4]cyclohepta[1,2-b]indol-2-amine (t28)
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Structure:
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Mitogen-activated protein kinase kinase kinase 14. Chain: a, b. Fragment: unp residues 330-680. Synonym: nf-kappa-beta-inducing kinase, hsnik, serine/threonine- protein kinase nik. Engineered: yes
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Source:
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Homo sapiens. Human. Organism_taxid: 9606. Gene: map3k14, nik
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Resolution:
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2.40Å
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R-factor:
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0.193
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R-free:
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0.228
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Authors:
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J.Liu,A.Sudom,Z.Wang
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Key ref:
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K.Li
et al.
(2013).
Inhibiting NF-κB-inducing kinase (NIK): discovery, structure-based design, synthesis, structure-activity relationship, and co-crystal structures.
Bioorg Med Chem Lett,
23,
1238-1244.
PubMed id:
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Date:
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13-Dec-12
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Release date:
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17-Apr-13
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PROCHECK
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Headers
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References
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Q99558
(M3K14_HUMAN) -
Mitogen-activated protein kinase kinase kinase 14 from Homo sapiens
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Seq:
Struc:
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947 a.a.
334 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.2.7.11.25
- mitogen-activated protein kinase kinase 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]
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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]
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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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Bioorg Med Chem Lett
23:1238-1244
(2013)
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PubMed id:
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Inhibiting NF-κB-inducing kinase (NIK): discovery, structure-based design, synthesis, structure-activity relationship, and co-crystal structures.
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K.Li,
L.R.McGee,
B.Fisher,
A.Sudom,
J.Liu,
S.M.Rubenstein,
M.K.Anwer,
T.D.Cushing,
Y.Shin,
M.Ayres,
F.Lee,
J.Eksterowicz,
P.Faulder,
B.Waszkowycz,
O.Plotnikova,
E.Farrelly,
S.H.Xiao,
G.Chen,
Z.Wang.
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ABSTRACT
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The discovery, structure-based design, synthesis, and optimization of NIK
inhibitors are described. Our work began with an HTS hit, imidazopyridinyl
pyrimidinamine 1. We utilized homology modeling and conformational analysis to
optimize the indole scaffold leading to the discovery of novel and potent
conformationally constrained inhibitors such as compounds 25 and 28. Compounds
25 and 31 were co-crystallized with NIK kinase domain to provide structural
insights.
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Links
