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PDBsum entry 2b0x
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Signaling protein
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PDB id
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2b0x
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References listed in PDB file
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Key reference
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Title
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Understanding the regulation mechanisms of paf receptor by agonists and antagonists: molecular modeling and molecular dynamics simulation studies.
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Authors
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C.Gui,
W.Zhu,
G.Chen,
X.Luo,
O.W.Liew,
C.M.Puah,
K.Chen,
H.Jiang.
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Ref.
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Proteins, 2007,
67,
41-52.
[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
percentage match of
96%.
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Abstract
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Platelet-activating factor receptor (PAFR) is a member of G-protein coupled
receptor (GPCR) superfamily. Understanding the regulation mechanisms of PAFR by
its agonists and antagonists at the atomic level is essential for designing PAFR
antagonists as drug candidates for treating PAF-mediated diseases. In this
study, a 3D model of PAFR was constructed by a hierarchical approach integrating
homology modeling, molecular docking and molecular dynamics (MD) simulations.
Based on the 3D model, regulation mechanisms of PAFR by agonists and antagonists
were investigated via three 8-ns MD simulations on the systems of apo-PAFR,
PAFR-PAF and PAFR-GB. The simulations revealed that binding of PAF to PAFR
triggers the straightening process of the kinked helix VI, leading to its
activated state. In contrast, binding of GB to PAFR locks PAFR in its inactive
state.
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Figure 3.
Figure 3. Structures of (a) model 2-PAF complex, (b) model 2-GB
complex, (c) model 3-PAF complex, (d) model 3-GB complex, (e)
PAF (top) and GB (bottom).
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Figure 9.
Figure 9. Schematic representation of the mechanism of PAFR
activation.
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The above figures are
reprinted
by permission from John Wiley & Sons, Inc.:
Proteins
(2007,
67,
41-52)
copyright 2007.
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