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PDBsum entry 4apc
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PDB id:
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Transferase
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Title:
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Crystal structure of human nima-related kinase 1 (nek1)
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Structure:
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Serine/threonine-protein kinase nek1. Chain: a, b. Fragment: kinase domain, residues 1-238. Synonym: never in mitosis a-related kinase 1, nima-related protein kinase 1, renal carcinoma antigen ny-ren-55. Engineered: yes. Mutation: yes
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Source:
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Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 469008.
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Resolution:
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2.10Å
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R-factor:
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0.216
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R-free:
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0.248
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Authors:
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J.M.Elkins,T.D.M.Hanchuk,D.V.Lovato,F.L.Basei,G.V.Meirelles,J.Kobarg, M.Szklarz,M.Vollmar,P.Mahajan,P.Rellos,Y.Zhang,T.Krojer,A.C.W.Pike, C.Bountra,C.Arrowsmith,A.Edwards,S.Knapp
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Key ref:
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T.D.Melo-Hanchuk
et al.
(2017).
NEK1 kinase domain structure and its dynamic protein interactome after exposure to Cisplatin.
Sci Rep,
7,
5445.
PubMed id:
DOI:
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Date:
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02-Apr-12
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Release date:
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25-Apr-12
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PROCHECK
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Headers
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References
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Q96PY6
(NEK1_HUMAN) -
Serine/threonine-protein kinase Nek1 from Homo sapiens
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Seq:
Struc:
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1258 a.a.
293 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 1 residue position (black
cross)
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Enzyme class:
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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]
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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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DOI no:
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Sci Rep
7:5445
(2017)
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PubMed id:
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NEK1 kinase domain structure and its dynamic protein interactome after exposure to Cisplatin.
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T.D.Melo-Hanchuk,
P.F.Slepicka,
G.V.Meirelles,
F.L.Basei,
D.V.Lovato,
D.C.Granato,
B.A.Pauletti,
R.R.Domingues,
A.F.P.Leme,
A.L.Pelegrini,
G.Lenz,
S.Knapp,
J.M.Elkins,
J.Kobarg.
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ABSTRACT
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NEK family kinases are serine/threonine kinases that have been functionally
implicated in the regulation of the disjunction of the centrosome, the assembly
of the mitotic spindle, the function of the primary cilium and the DNA damage
response. NEK1 shows pleiotropic functions and has been found to be mutated in
cancer cells, ciliopathies such as the polycystic kidney disease, as well as in
the genetic diseases short-rib thoracic dysplasia, Mohr-syndrome and amyotrophic
lateral sclerosis. NEK1 is essential for the ionizing radiation DNA damage
response and priming of the ATR kinase and of Rad54 through phosphorylation.
Here we report on the structure of the kinase domain of human NEK1 in its apo-
and ATP-mimetic inhibitor bound forms. The inhibitor bound structure may allow
the design of NEK specific chemo-sensitizing agents to act in conjunction with
chemo- or radiation therapy of cancer cells. Furthermore, we characterized the
dynamic protein interactome of NEK1 after DNA damage challenge with cisplatin.
Our data suggest that NEK1 and its interaction partners trigger the DNA damage
pathways responsible for correcting DNA crosslinks.
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