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PDBsum entry 3k2l
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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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Crystal structure of dual-specificity tyrosine phosphorylation regulated kinase 2 (dyrk2)
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Structure:
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Dual specificity tyrosine-phosphorylation-regulated kinase 2. Chain: a. Fragment: unp residues 146-552. Synonym: dyrk2. Engineered: yes
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Source:
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Homo sapiens. Human. Organism_taxid: 9606. Gene: dyrk2. Expressed in: escherichia coli. Expression_system_taxid: 469008.
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Resolution:
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2.36Å
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R-factor:
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0.228
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R-free:
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0.288
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Authors:
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P.Filippakopoulos,V.Myrianthopoulos,M.Soundararajan,T.Krojer,E.Hapka, O.Fedorov,G.Berridge,J.Wang,L.Shrestha,A.C.W.Pike,E.Ugochukwu,F.Von Delft,C.H.Arrowsmith,A.Edwards,J.Weigelt,C.Bountra,E.Mikros,S.Knapp, Structural Genomics Consortium (Sgc)
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Key ref:
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M.Soundararajan
et al.
(2013).
Structures of Down syndrome kinases, DYRKs, reveal mechanisms of kinase activation and substrate recognition.
Structure,
21,
986-996.
PubMed id:
DOI:
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Date:
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30-Sep-09
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Release date:
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13-Oct-09
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PROCHECK
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Headers
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References
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Q92630
(DYRK2_HUMAN) -
Dual specificity tyrosine-phosphorylation-regulated kinase 2 from Homo sapiens
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Seq:
Struc:
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601 a.a.
407 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 11 residue positions (black
crosses)
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Enzyme class:
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E.C.2.7.12.1
- dual-specificity 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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3.
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L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[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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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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Structure
21:986-996
(2013)
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PubMed id:
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Structures of Down syndrome kinases, DYRKs, reveal mechanisms of kinase activation and substrate recognition.
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M.Soundararajan,
A.K.Roos,
P.Savitsky,
P.Filippakopoulos,
A.N.Kettenbach,
J.V.Olsen,
S.A.Gerber,
J.Eswaran,
S.Knapp,
J.M.Elkins.
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ABSTRACT
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Dual-specificity tyrosine-(Y)-phosphorylation-regulated kinases (DYRKs) play key
roles in brain development, regulation of splicing, and apoptosis, and are
potential drug targets for neurodegenerative diseases and cancer. We present
crystal structures of one representative member of each DYRK subfamily: DYRK1A
with an ATP-mimetic inhibitor and consensus peptide, and DYRK2 including NAPA
and DH (DYRK homology) box regions. The current activation model suggests that
DYRKs are Ser/Thr kinases that only autophosphorylate the second tyrosine of the
activation loop YxY motif during protein translation. The structures explain the
roles of this tyrosine and of the DH box in DYRK activation and provide a
structural model for DYRK substrate recognition. Phosphorylation of a library of
naturally occurring peptides identified substrate motifs that lack proline in
the P+1 position, suggesting that DYRK1A is not a strictly proline-directed
kinase. Our data also show that DYRK1A wild-type and Y321F mutant retain
tyrosine autophosphorylation activity.
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Links
