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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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Contents |
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* Residue conservation analysis
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PDB id:
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Cell adhesion
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Title:
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Crystal structure of wild type lfa1 i domain complexed with isoflurane
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Structure:
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Integrin alpha-l. Chain: a, b, c. Fragment: unp residues 153-332, vwfa domain, i domain. Synonym: leukocyte adhesion glycoprotein lfa-1 alpha chain, lfa-1a, leukocyte function-associated molecule 1 alpha chain, cd11 antigen- like family member a. Engineered: yes
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Source:
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Homo sapiens. Human. Organism_taxid: 9606. Gene: cd11a, integrin lfa1, itgal. Expressed in: escherichia coli. Expression_system_taxid: 562.
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Resolution:
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1.60Å
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R-factor:
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0.154
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R-free:
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0.181
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Authors:
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H.Zhang,J.-H.Wang
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Key ref:
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H.Zhang
et al.
(2009).
Crystal structure of isoflurane bound to integrin LFA-1 supports a unified mechanism of volatile anesthetic action in the immune and central nervous systems.
Faseb J,
23,
2735-2740.
PubMed id:
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Date:
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07-Nov-08
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Release date:
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23-Jun-09
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PROCHECK
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Headers
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References
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P20701
(ITAL_HUMAN) -
Integrin alpha-L from Homo sapiens
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Seq:
Struc:
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1170 a.a.
180 a.a.*
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Key: |
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PfamA domain |
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Secondary structure |
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CATH domain |
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*
PDB and UniProt seqs differ
at 1 residue position (black
cross)
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Faseb J
23:2735-2740
(2009)
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PubMed id:
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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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H.Zhang,
N.S.Astrof,
J.H.Liu,
J.H.Wang,
M.Shimaoka.
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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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Literature references that cite this PDB file's key reference
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PubMed id
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Reference
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H.Nury,
C.Van Renterghem,
Y.Weng,
A.Tran,
M.Baaden,
V.Dufresne,
J.P.Changeux,
J.M.Sonner,
M.Delarue,
and
P.J.Corringer
(2011).
X-ray structures of general anaesthetics bound to a pentameric ligand-gated ion channel.
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Nature,
469,
428-431.
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PDB codes:
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K.Yuki,
S.G.Soriano,
and
M.Shimaoka
(2011).
Sedative drug modulates T-cell and lymphocyte function-associated antigen-1 function.
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Anesth Analg,
112,
830-838.
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D.Cox,
M.Brennan,
and
N.Moran
(2010).
Integrins as therapeutic targets: lessons and opportunities.
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Nat Rev Drug Discov,
9,
804-820.
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R.G.Eckenhoff,
J.Xi,
M.Shimaoka,
A.Bhattacharji,
M.Covarrubias,
and
W.P.Dailey
(2010).
Azi-isoflurane, a Photolabel Analog of the Commonly Used Inhaled General Anesthetic Isoflurane.
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ACS Chem Neurosci,
1,
139-145.
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Y.Lu,
Y.Wang,
and
W.Zhu
(2010).
Nonbonding interactions of organic halogens in biological systems: implications for drug discovery and biomolecular design.
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Phys Chem Chem Phys,
12,
4543-4551.
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The most recent references are shown first.
Citation data come partly from CiteXplore and partly
from an automated harvesting procedure. Note that this is likely to be
only a partial list as not all journals are covered by
either method. However, we are continually building up the citation data
so more and more references will be included with time.
Where a reference describes a PDB structure, the PDB
codes are
shown on the right.
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Links
