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PDBsum entry 3g51
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References listed in PDB file
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Key reference
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Title
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Structural diversity of the active n-Terminal kinase domain of p90 ribosomal s6 kinase 2.
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Authors
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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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Ref.
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Plos One, 2009,
4,
e8044.
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PubMed id
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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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