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PDBsum entry 3f78
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Cell adhesion
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PDB id
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3f78
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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 isoflurane bound to integrin lfa-1 supports a unified mechanism of volatile anesthetic action in the immune and central nervous systems.
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Authors
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H.Zhang,
N.S.Astrof,
J.H.Liu,
J.H.Wang,
M.Shimaoka.
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Ref.
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Faseb J, 2009,
23,
2735-2740.
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PubMed id
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Abstract
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Volatile anesthetics (VAs), such as isoflurane, induce a general anesthetic
state by binding to specific targets (i.e., ion channels) in the central nervous
system (CNS). Simultaneously, VAs modulate immune functions, possibly via direct
interaction with alternative targets on leukocytes. One such target, the
integrin lymphocyte function-associated antigen-1 (LFA-1), has been shown
previously to be inhibited by isoflurane. A better understanding of the
mechanism by which isoflurane alters protein function requires the detailed
information about the drug-protein interaction at an atomic level. Here, we
describe the crystal structure of the LFA-1 ligand-binding domain (I domain) in
complex with isoflurane at 1.6 A. We discovered that isoflurane binds to an
allosteric cavity previously implicated as critical for the transition of LFA-1
from the low- to the high-affinity state. The isoflurane binding site in the I
domain involves an array of amphiphilic interactions, thereby resembling a
"common anesthetic binding motif" previously predicted for authentic VA binding
sites. These results suggest that the allosteric modulation of protein function
by isoflurane, as demonstrated for the integrin LFA-1, might represent a unified
mechanism shared by the interactions of volatile anesthetics with targets in the
CNS.
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