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PDBsum entry 4dn5
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PDB id:
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Transferase
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Title:
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Crystal structure of nf-kb-inducing kinase (nik)
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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. Mutation: yes
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Source:
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Homo sapiens. Human. Organism_taxid: 9606. Gene: map3k14, nf-kb-inducing kinase, nik. Expressed in: spodoptera frugiperda. Expression_system_taxid: 7108. Expression_system_cell_line: sf9.
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Resolution:
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2.50Å
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R-factor:
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0.184
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R-free:
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0.222
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Authors:
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X.Min,J.Liu,A.Sudom,N.P.Walker,Z.Wang
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Key ref:
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J.Liu
et al.
(2012).
Structure of the nuclear factor κB-inducing kinase (NIK) kinase domain reveals a constitutively active conformation.
J Biol Chem,
287,
27326-27334.
PubMed id:
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Date:
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08-Feb-12
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Release date:
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27-Jun-12
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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.
331 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]
Bound ligand (Het Group name = )
matches with 93.75% similarity
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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]
Bound ligand (Het Group name = )
matches with 93.75% similarity
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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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J Biol Chem
287:27326-27334
(2012)
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PubMed id:
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Structure of the nuclear factor κB-inducing kinase (NIK) kinase domain reveals a constitutively active conformation.
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J.Liu,
A.Sudom,
X.Min,
Z.Cao,
X.Gao,
M.Ayres,
F.Lee,
P.Cao,
S.Johnstone,
O.Plotnikova,
N.Walker,
G.Chen,
Z.Wang.
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ABSTRACT
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NF-κB-inducing kinase (NIK) is a central component in the non-canonical NF-κB
signaling pathway. Excessive NIK activity is implicated in various disorders,
such as autoimmune conditions and cancers. Here, we report the first crystal
structure of truncated human NIK in complex with adenosine
5'-O-(thiotriphosphate) at a resolution of 2.5 Å. This truncated protein is a
catalytically active construct, including an N-terminal extension of 60 residues
prior to the kinase domain, the kinase domain, and 20 residues afterward. The
structure reveals that the NIK kinase domain assumes an active conformation in
the absence of any phosphorylation. Analysis of the structure uncovers a unique
role for the N-terminal extension sequence, which stabilizes helix αC in the
active orientation and keeps the kinase domain in the catalytically competent
conformation. Our findings shed light on the long-standing debate over whether
NIK is a constitutively active kinase. They also provide a molecular basis for
the recent observation of gain-of-function activity for an N-terminal deletion
mutant (ΔN324) of NIK, leading to constitutive non-canonical NF-κB signaling
with enhanced B-cell adhesion and apoptosis resistance.
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Links
