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PDBsum entry 4z07
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References listed in PDB file
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Key reference
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Title
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Crystal structure of pkg I:cgmp complex reveals a cgmp-Mediated dimeric interface that facilitates cgmp-Induced activation.
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Authors
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J.J.Kim,
R.Lorenz,
S.T.Arold,
A.S.Reger,
B.Sankaran,
D.E.Casteel,
F.W.Herberg,
C.Kim.
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Ref.
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Structure, 2016,
24,
710-720.
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PubMed id
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Abstract
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Cyclic guanosine monophosphate (cGMP)-dependent protein kinase (PKG) is a key
regulator of smooth muscle and vascular tone and represents an important drug
target for treating hypertensive diseases and erectile dysfunction. Despite its
importance, its activation mechanism is not fully understood. To understand the
activation mechanism, we determined a 2.5 Å crystal structure of the PKG I
regulatory (R) domain bound with cGMP, which represents the activated state.
Although we used a monomeric domain for crystallization, the structure reveals
that two R domains form a symmetric dimer where the cGMP bound at high-affinity
pockets provide critical dimeric contacts. Small-angle X-ray scattering and
mutagenesis support this dimer model, suggesting that the dimer interface
modulates kinase activation. Finally, structural comparison with the homologous
cyclic AMP-dependent protein kinase reveals that PKG is drastically different
from protein kinase A in its active conformation, suggesting a novel activation
mechanism for PKG.
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