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PDBsum entry 3g51
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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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Structural diversity of the active conformation of the n-terminal kinase domain of p90 ribosomal s6 kinase 2
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Structure:
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Ribosomal protein s6 kinase alpha-3. Chain: a. Synonym: s6k-alpha 3, 90 kda ribosomal protein s6 kinase 3, p90-rsk 3, ribosomal s6 kinase 2, rsk-2, pp90rsk2, map kinase-activated protein kinase 1b, mapkapk1b. Engineered: yes
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Source:
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Mus musculus. Mouse. Organism_taxid: 10090. Gene: mus musculus ribosomal protein s6 kinase 2, rps6ka-rs1, rps6ka3, rsk2. Expressed in: escherichia coli. Expression_system_taxid: 562.
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Resolution:
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1.80Å
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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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I.Kurinov
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Key ref:
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M.Malakhova
et al.
(2009).
Structural diversity of the active N-terminal kinase domain of p90 ribosomal S6 kinase 2.
Plos One,
4,
e8044.
PubMed id:
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Date:
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04-Feb-09
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Release date:
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15-Dec-09
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PROCHECK
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Headers
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References
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P18654
(KS6A3_MOUSE) -
Ribosomal protein S6 kinase alpha-3 from Mus musculus
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Seq:
Struc:
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740 a.a.
280 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.2.7.11.1
- 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]
Bound ligand (Het Group name = )
matches with 81.25% similarity
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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]
Bound ligand (Het Group name = )
matches with 81.25% similarity
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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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Plos One
4:e8044
(2009)
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PubMed id:
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Structural diversity of the active N-terminal kinase domain of p90 ribosomal S6 kinase 2.
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M.Malakhova,
I.Kurinov,
K.Liu,
D.Zheng,
I.D'Angelo,
J.H.Shim,
V.Steinman,
A.M.Bode,
Z.Dong.
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ABSTRACT
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The p90 ribosomal protein kinase 2 (RSK2) is a highly expressed Ser/Thr kinase
activated by growth factors and is involved in cancer cell proliferation and
tumor promoter-induced cell transformation. RSK2 possesses two non-identical
kinase domains, and the structure of its N-terminal domain (NTD), which is
responsible for phosphorylation of a variety of substrates, is unknown. The
crystal structure of the NTD RSK2 was determined at 1.8 A resolution in complex
with AMP-PNP. The N-terminal kinase domain adopted a unique active conformation
showing a significant structural diversity of the kinase domain compared to
other kinases. The NTD RSK2 possesses a three-stranded betaB-sheet inserted in
the N-terminal lobe, resulting in displacement of the alphaC-helix and
disruption of the Lys-Glu interaction, classifying the kinase conformation as
inactive. The purified protein was phosphorylated at Ser227 in the T-activation
loop and exhibited in vitro kinase activity. A key characteristic is the
appearance of a new contact between Lys216 (betaB-sheet) and the beta-phosphate
of AMP-PNP. Mutation of this lysine to alanine impaired both NTDs in vitro and
full length RSK2 ex vivo activity, emphasizing the importance of this
interaction. Even though the N-terminal lobe undergoes structural
re-arrangement, it possesses an intact hydrophobic groove formed between the
alphaC-helix, the beta4-strand, and the betaB-sheet junction, which is occupied
by the N-terminal tail. The presence of a unique betaB-sheet insert in the
N-lobe suggests a different type of activation mechanism for RSK2.
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Links
