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PDBsum entry 1vzo
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Contents |
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* Residue conservation analysis
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References listed in PDB file
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Key reference
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Title
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The structure of msk1 reveals a novel autoinhibitory conformation for a dual kinase protein.
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Authors
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K.J.Smith,
P.S.Carter,
A.Bridges,
P.Horrocks,
C.Lewis,
G.Pettman,
A.Clarke,
M.Brown,
J.Hughes,
M.Wilkinson,
B.Bax,
A.Reith.
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Ref.
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Structure, 2004,
12,
1067-1077.
[DOI no: ]
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PubMed id
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Note In the PDB file this reference is
annotated as "TO BE PUBLISHED".
The citation details given above were identified by an automated
search of PubMed on title and author
names, giving a
perfect match.
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Abstract
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Mitogen and stress-activated kinase-1 (MSK1) is a serine/threonine protein
kinase that is activated by either p38 or p42ERK MAPKs in response to stress or
mitogenic extracellular stimuli. MSK1 belongs to a family of protein kinases
that contain two distinct kinase domains in one polypeptide chain. We report the
1.8 A crystal structure of the N-terminal kinase domain of MSK1. The crystal
structure reveals a unique inactive conformation with the ATP binding site
blocked by the nucleotide binding loop. This inactive conformation is stabilized
by the formation of a new three-stranded beta sheet on the N lobe of the kinase
domain. The three beta strands come from residues at the N terminus of the
kinase domain, what would be the alphaB helix in the active conformation, and
the activation loop. The new three-stranded beta sheet occupies a position
equivalent to the N terminus of the alphaC helix in active protein kinases.
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Figure 3.
Figure 3. Overall Structure of MSK1 and PKA(A) and (B) are
ribbon diagrams of MSK1 N-terminal domain, (C) and (D) are
ribbon diagrams of PKA (PDB code 1ATP) with AMP-PNP shown as red
ball-and-sticks. Views (B) and (D) are of the back of the kinase
and are rotated 90° relative to (A) and (C) about the vertical
axis. The nucleotide binding loop of MSK1 and PKA is shown in
red and the activation loop is shown in blue. The aB helix and
aChelix of PKA (residues 75-104) and the equivalent residues in
MSK1 (residues 84-115) are shown in orange. The three stranded b
sheet motif on the surface on the MSK1 N lobe is clearly visible
in (B). The three strands are from the N terminus (green),
aBhelix (orange), and the activation loop (blue).
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The above figure is
reprinted
by permission from Cell Press:
Structure
(2004,
12,
1067-1077)
copyright 2004.
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