 |
PDBsum entry 4qfg
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Signaling protein/inhibitor
|
PDB id
|
|
|
|
4qfg
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
Contents |
 |
|
|
|
|
|
|
|
|
|
|
|
366 a.a.
|
|
|
|
|
|
|
|
|
|
|
161 a.a.
|
|
|
|
|
|
|
|
|
|
|
287 a.a.
|
|
|
|
|
|
|
|
|
|
|
|
|
|
References listed in PDB file
|
|
|
Key reference
|
|
|
Title
|
|
Structural basis for ampk activation: natural and synthetic ligands regulate kinase activity from opposite poles by different molecular mechanisms.
|
|
|
Authors
|
|
M.F.Calabrese,
F.Rajamohan,
M.S.Harris,
N.L.Caspers,
R.Magyar,
J.M.Withka,
H.Wang,
K.A.Borzilleri,
P.V.Sahasrabudhe,
L.R.Hoth,
K.F.Geoghegan,
S.Han,
J.Brown,
T.A.Subashi,
A.R.Reyes,
R.K.Frisbie,
J.Ward,
R.A.Miller,
J.A.Landro,
A.T.Londregan,
P.A.Carpino,
S.Cabral,
A.C.Smith,
E.L.Conn,
K.O.Cameron,
X.Qiu,
R.G.Kurumbail.
|
|
|
Ref.
|
|
Structure, 2014,
22,
1161-1172.
[DOI no: ]
|
|
|
PubMed id
|
|
|
|
|
|
Abstract
|
|
|
AMP-activated protein kinase (AMPK) is a principal metabolic regulator affecting
growth and response to cellular stress. Comprised of catalytic and regulatory
subunits, each present in multiple forms, AMPK is best described as a family of
related enzymes. In recent years, AMPK has emerged as a desirable target for
modulation of numerous diseases, yet clinical therapies remain elusive.
Challenges result, in part, from an incomplete understanding of the structure
and function of full-length heterotrimeric complexes. In this work, we provide
the full-length structure of the widely expressed α1β1γ1 isoform of mammalian
AMPK, along with detailed kinetic and biophysical characterization. We
characterize binding of the broadly studied synthetic activator A769662 and its
analogs. Our studies follow on the heels of the recent disclosure of the
α2β1γ1 structure and provide insight into the distinct molecular mechanisms
of AMPK regulation by AMP and A769662.
|
|
|
|
|
|
|
