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Contents |
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* Residue conservation analysis
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Gene Ontology (GO) functional annotation
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Cellular component
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cAMP-dependent protein kinase complex
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1 term
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Biological process
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regulation of protein amino acid phosphorylation
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1 term
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Biochemical function
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cAMP-dependent protein kinase regulator activity
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1 term
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DOI no:
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Science
269:807-813
(1995)
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PubMed id:
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Regulatory subunit of protein kinase A: structure of deletion mutant with cAMP binding domains.
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Y.Su,
W.R.Dostmann,
F.W.Herberg,
K.Durick,
N.H.Xuong,
L.Ten Eyck,
S.S.Taylor,
K.I.Varughese.
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ABSTRACT
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In the molecular scheme of living organisms, adenosine 3',5'-monophosphate
(cyclic AMP or cAMP) has been a universal second messenger. In eukaryotic cells,
the primary receptors for cAMP are the regulatory subunits of cAMP-dependent
protein kinase. The crystal structure of a 1-91 deletion mutant of the type I
alpha regulatory subunit was refined to 2.8 A resolution. Each of the two tandem
cAMP binding domains provides an extensive network of hydrogen bonds that buries
the cyclic phosphate and the ribose between two beta strands that are linked by
a short alpha helix. Each adenine base stacks against an aromatic ring that lies
outside the beta barrel. This structure provides a molecular basis for
understanding how cAMP binds cooperatively to its receptor protein, thus
mediating activation of the kinase.
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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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A.Cukkemane,
R.Seifert,
and
U.B.Kaupp
(2011).
Cooperative and uncooperative cyclic-nucleotide-gated ion channels.
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Trends Biochem Sci, 36,
55-64.
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J.H.Lee,
S.Li,
T.Liu,
S.Hsu,
C.Kim,
V.L.Woods,
and
D.E.Casteel
(2011).
The amino terminus of cGMP-dependent protein kinase Iβ increases the dynamics of the protein's cGMP-binding pockets.
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Int J Mass Spectrom, 302,
44-52.
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N.Wurtz,
C.Chapus,
J.Desplans,
and
D.Parzy
(2011).
cAMP-dependent protein kinase from Plasmodium falciparum: an update.
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| |
Parasitology, 138,
1.
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S.Schünke,
M.Stoldt,
J.Lecher,
U.B.Kaupp,
and
D.Willbold
(2011).
Structural insights into conformational changes of a cyclic nucleotide-binding domain in solution from Mesorhizobium loti K1 channel.
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Proc Natl Acad Sci U S A, 108,
6121-6126.
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PDB code:
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J.Rinaldi,
J.Wu,
J.Yang,
C.Y.Ralston,
B.Sankaran,
S.Moreno,
and
S.S.Taylor
(2010).
Structure of yeast regulatory subunit: a glimpse into the evolution of PKA signaling.
|
| |
Structure, 18,
1471-1482.
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PDB code:
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O.N.Rogacheva,
A.V.Popov,
E.V.Savvateeva-Popova,
V.E.Stefanov,
and
B.F.Shchegolev
(2010).
Thermodynamic analysis of protein kinase A Ialpha activation.
|
| |
Biochemistry (Mosc), 75,
233-241.
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T.J.Sjoberg,
A.P.Kornev,
and
S.S.Taylor
(2010).
Dissecting the cAMP-inducible allosteric switch in protein kinase A RIalpha.
|
| |
Protein Sci, 19,
1213-1221.
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PDB code:
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R.Das,
S.Chowdhury,
M.T.Mazhab-Jafari,
S.Sildas,
R.Selvaratnam,
and
G.Melacini
(2009).
Dynamically driven ligand selectivity in cyclic nucleotide binding domains.
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| |
J Biol Chem, 284,
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S.Naviglio,
M.Caraglia,
A.Abbruzzese,
E.Chiosi,
D.Di Gesto,
M.Marra,
M.Romano,
A.Sorrentino,
L.Sorvillo,
A.Spina,
and
G.Illiano
(2009).
Protein kinase A as a biological target in cancer therapy.
|
| |
Expert Opin Ther Targets, 13,
83-92.
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|
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|
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S.Schünke,
M.Stoldt,
K.Novak,
U.B.Kaupp,
and
D.Willbold
(2009).
Solution structure of the Mesorhizobium loti K1 channel cyclic nucleotide-binding domain in complex with cAMP.
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EMBO Rep, 10,
729-735.
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PDB code:
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T.Endoh,
and
J.N.Engel
(2009).
CbpA: a polarly localized novel cyclic AMP-binding protein in Pseudomonas aeruginosa.
|
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J Bacteriol, 191,
7193-7205.
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T.I.Brelidze,
A.E.Carlson,
and
W.N.Zagotta
(2009).
Absence of direct cyclic nucleotide modulation of mEAG1 and hERG1 channels revealed with fluorescence and electrophysiological methods.
|
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J Biol Chem, 284,
27989-27997.
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T.Tsalkova,
D.K.Blumenthal,
F.C.Mei,
M.A.White,
and
X.Cheng
(2009).
Mechanism of Epac activation: structural and functional analyses of Epac2 hinge mutants with constitutive and reduced activities.
|
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J Biol Chem, 284,
23644-23651.
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A.P.Kornev,
S.S.Taylor,
and
L.F.Ten Eyck
(2008).
A generalized allosteric mechanism for cis-regulated cyclic nucleotide binding domains.
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PLoS Comput Biol, 4,
e1000056.
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G.G.Holz,
O.G.Chepurny,
and
F.Schwede
(2008).
Epac-selective cAMP analogs: new tools with which to evaluate the signal transduction properties of cAMP-regulated guanine nucleotide exchange factors.
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Cell Signal, 20,
10-20.
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H.J.Newton,
F.M.Sansom,
J.Dao,
C.Cazalet,
H.Bruggemann,
C.Albert-Weissenberger,
C.Buchrieser,
N.P.Cianciotto,
and
E.L.Hartland
(2008).
Significant role for ladC in initiation of Legionella pneumophila infection.
|
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Infect Immun, 76,
3075-3085.
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H.Rehmann,
E.Arias-Palomo,
M.A.Hadders,
F.Schwede,
O.Llorca,
and
J.L.Bos
(2008).
Structure of Epac2 in complex with a cyclic AMP analogue and RAP1B.
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Nature, 455,
124-127.
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PDB code:
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S.L.Altieri,
G.M.Clayton,
W.R.Silverman,
A.O.Olivares,
E.M.De la Cruz,
L.R.Thomas,
and
J.H.Morais-Cabral
(2008).
Structural and energetic analysis of activation by a cyclic nucleotide binding domain.
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J Mol Biol, 381,
655-669.
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PDB codes:
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S.S.Taylor,
C.Kim,
C.Y.Cheng,
S.H.Brown,
J.Wu,
and
N.Kannan
(2008).
Signaling through cAMP and cAMP-dependent protein kinase: diverse strategies for drug design.
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| |
Biochim Biophys Acta, 1784,
16-26.
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S.Schweinsberg,
D.Moll,
N.C.Burghardt,
C.Hahnefeld,
F.Schwede,
B.Zimmermann,
S.Drewianka,
L.Werner,
F.Kleinjung,
H.G.Genieser,
J.Schuchhardt,
and
F.W.Herberg
(2008).
Systematic interpretation of cyclic nucleotide binding studies using KinetXBase.
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Proteomics, 8,
1212-1220.
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X.Cheng,
Z.Ji,
T.Tsalkova,
and
F.Mei
(2008).
Epac and PKA: a tale of two intracellular cAMP receptors.
|
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Acta Biochim Biophys Sin (Shanghai), 40,
651-662.
|
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A.Scholten,
H.Fuss,
A.J.Heck,
and
W.R.Dostmann
(2007).
The hinge region operates as a stability switch in cGMP-dependent protein kinase I alpha.
|
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FEBS J, 274,
2274-2286.
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C.Kim,
C.Y.Cheng,
S.A.Saldanha,
and
S.S.Taylor
(2007).
PKA-I holoenzyme structure reveals a mechanism for cAMP-dependent activation.
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Cell, 130,
1032-1043.
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PDB code:
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D.Moll,
S.Schweinsberg,
C.Hammann,
and
F.W.Herberg
(2007).
Comparative thermodynamic analysis of cyclic nucleotide binding to protein kinase A.
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Biol Chem, 388,
163-172.
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E.M.Rubenstein,
and
M.C.Schmidt
(2007).
Mechanisms regulating the protein kinases of Saccharomyces cerevisiae.
|
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Eukaryot Cell, 6,
571-583.
|
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G.E.Flynn,
K.D.Black,
L.D.Islas,
B.Sankaran,
and
W.N.Zagotta
(2007).
Structure and rearrangements in the carboxy-terminal region of SpIH channels.
|
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Structure, 15,
671-682.
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PDB codes:
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H.Rehmann,
A.Wittinghofer,
and
J.L.Bos
(2007).
Capturing cyclic nucleotides in action: snapshots from crystallographic studies.
|
| |
Nat Rev Mol Cell Biol, 8,
63-73.
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J.Clardy,
and
S.F.Brady
(2007).
Cyclic AMP directly activates NasP, an N-acyl amino acid antibiotic biosynthetic enzyme cloned from an uncultured beta-proteobacterium.
|
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J Bacteriol, 189,
6487-6489.
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J.W.Scott,
F.A.Ross,
J.K.Liu,
and
D.G.Hardie
(2007).
Regulation of AMP-activated protein kinase by a pseudosubstrate sequence on the gamma subunit.
|
| |
EMBO J, 26,
806-815.
|
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J.Wu,
S.H.Brown,
S.von Daake,
and
S.S.Taylor
(2007).
PKA type IIalpha holoenzyme reveals a combinatorial strategy for isoform diversity.
|
| |
Science, 318,
274-279.
|
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PDB code:
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M.Abu-Abed,
R.Das,
L.Wang,
and
G.Melacini
(2007).
Definition of an electrostatic relay switch critical for the cAMP-dependent activation of protein kinase A as revealed by the D170A mutant of RIalpha.
|
| |
Proteins, 69,
112-124.
|
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M.E.Doyle,
and
J.M.Egan
(2007).
Mechanisms of action of glucagon-like peptide 1 in the pancreas.
|
| |
Pharmacol Ther, 113,
546-593.
|
|
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|
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|
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N.Kannan,
J.Wu,
G.S.Anand,
S.Yooseph,
A.F.Neuwald,
C.J.Venter,
and
S.S.Taylor
(2007).
Evolution of allostery in the cyclic nucleotide binding module.
|
| |
Genome Biol, 8,
R264.
|
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|
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R.Das,
V.Esposito,
M.Abu-Abed,
G.S.Anand,
S.S.Taylor,
and
G.Melacini
(2007).
cAMP activation of PKA defines an ancient signaling mechanism.
|
| |
Proc Natl Acad Sci U S A, 104,
93-98.
|
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|
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B.A.Manjasetty,
K.Büssow,
M.Fieber-Erdmann,
Y.Roske,
J.Gobom,
C.Scheich,
F.Götz,
F.H.Niesen,
and
U.Heinemann
(2006).
Crystal structure of Homo sapiens PTD012 reveals a zinc-containing hydrolase fold.
|
| |
Protein Sci, 15,
914-920.
|
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PDB code:
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D.Vigil,
J.H.Lin,
C.A.Sotriffer,
J.K.Pennypacker,
J.A.McCammon,
and
S.S.Taylor
(2006).
A simple electrostatic switch important in the activation of type I protein kinase A by cyclic AMP.
|
| |
Protein Sci, 15,
113-121.
|
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|
|
|
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H.Rehmann,
J.Das,
P.Knipscheer,
A.Wittinghofer,
and
J.L.Bos
(2006).
Structure of the cyclic-AMP-responsive exchange factor Epac2 in its auto-inhibited state.
|
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Nature, 439,
625-628.
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PDB code:
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J.Gullingsrud,
C.Kim,
S.S.Taylor,
and
J.A.McCammon
(2006).
Dynamic binding of PKA regulatory subunit RI alpha.
|
| |
Structure, 14,
141-149.
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J.Trewhella
(2006).
Structural themes and variations in protein kinase A as seen by small-angle scattering and neutron contrast variation.
|
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Eur Biophys J, 35,
585-589.
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K.B.Craven,
and
W.N.Zagotta
(2006).
CNG and HCN channels: two peas, one pod.
|
| |
Annu Rev Physiol, 68,
375-401.
|
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|
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M.Berrera,
S.Pantano,
and
P.Carloni
(2006).
cAMP Modulation of the cytoplasmic domain in the HCN2 channel investigated by molecular simulations.
|
| |
Biophys J, 90,
3428-3433.
|
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R.L.Brown,
T.Strassmaier,
J.D.Brady,
and
J.W.Karpen
(2006).
The pharmacology of cyclic nucleotide-gated channels: emerging from the darkness.
|
| |
Curr Pharm Des, 12,
3597-3613.
|
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|
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S.Yu,
F.Fan,
S.C.Flores,
F.Mei,
and
X.Cheng
(2006).
Dissecting the mechanism of Epac activation via hydrogen-deuterium exchange FT-IR and structural modeling.
|
| |
Biochemistry, 45,
15318-15326.
|
|
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C.Hahnefeld,
D.Moll,
M.Goette,
and
F.W.Herberg
(2005).
Rearrangements in a hydrophobic core region mediate cAMP action in the regulatory subunit of PKA.
|
| |
Biol Chem, 386,
623-631.
|
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|
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|
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D.Bridges,
M.E.Fraser,
and
G.B.Moorhead
(2005).
Cyclic nucleotide binding proteins in the Arabidopsis thaliana and Oryza sativa genomes.
|
| |
BMC Bioinformatics, 6,
6.
|
|
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|
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|
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D.Law,
M.Hotchko,
and
L.Ten Eyck
(2005).
Progress in computation and amide hydrogen exchange for prediction of protein-protein complexes.
|
| |
Proteins, 60,
302-307.
|
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|
|
H.M.Berman,
L.F.Ten Eyck,
D.S.Goodsell,
N.M.Haste,
A.Kornev,
and
S.S.Taylor
(2005).
The cAMP binding domain: an ancient signaling module.
|
| |
Proc Natl Acad Sci U S A, 102,
45-50.
|
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|
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|
|
K.L.Dodge-Kafka,
J.Soughayer,
G.C.Pare,
J.J.Carlisle Michel,
L.K.Langeberg,
M.S.Kapiloff,
and
J.D.Scott
(2005).
The protein kinase A anchoring protein mAKAP coordinates two integrated cAMP effector pathways.
|
| |
Nature, 437,
574-578.
|
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|
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M.Baruscotti,
A.Bucchi,
and
D.Difrancesco
(2005).
Physiology and pharmacology of the cardiac pacemaker ("funny") current.
|
| |
Pharmacol Ther, 107,
59-79.
|
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|
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|
|
Y.Kimura,
H.Nakato,
K.Ishibashi,
and
S.Kobayashi
(2005).
A Myxococcus xanthus CbpB containing two cAMP-binding domains is involved in temperature and osmotic tolerances.
|
| |
FEMS Microbiol Lett, 244,
75-83.
|
|
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|
|
|
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G.M.Clayton,
W.R.Silverman,
L.Heginbotham,
and
J.H.Morais-Cabral
(2004).
Structural basis of ligand activation in a cyclic nucleotide regulated potassium channel.
|
| |
Cell, 119,
615-627.
|
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PDB codes:
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J.W.Scott,
S.A.Hawley,
K.A.Green,
M.Anis,
G.Stewart,
G.A.Scullion,
D.G.Norman,
and
D.G.Hardie
(2004).
CBS domains form energy-sensing modules whose binding of adenosine ligands is disrupted by disease mutations.
|
| |
J Clin Invest, 113,
274-284.
|
|
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|
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|
|
J.Wu,
S.Brown,
N.H.Xuong,
and
S.S.Taylor
(2004).
RIalpha subunit of PKA: a cAMP-free structure reveals a hydrophobic capping mechanism for docking cAMP into site B.
|
| |
Structure, 12,
1057-1065.
|
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PDB code:
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|
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|
|
G.S.Anand,
D.Law,
J.G.Mandell,
A.N.Snead,
I.Tsigelny,
S.S.Taylor,
L.F.Ten Eyck,
and
E.A.Komives
(2003).
Identification of the protein kinase A regulatory RIalpha-catalytic subunit interface by amide H/2H exchange and protein docking.
|
| |
Proc Natl Acad Sci U S A, 100,
13264-13269.
|
|
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PDB code:
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|
H.Rehmann,
B.Prakash,
E.Wolf,
A.Rueppel,
J.de Rooij,
J.L.Bos,
and
A.Wittinghofer
(2003).
Structure and regulation of the cAMP-binding domains of Epac2.
|
| |
Nat Struct Biol, 10,
26-32.
|
|
|
PDB code:
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J.L.Bos
(2003).
Epac: a new cAMP target and new avenues in cAMP research.
|
| |
Nat Rev Mol Cell Biol, 4,
733-738.
|
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|
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|
|
K.M.Zawadzki,
C.P.Pan,
M.D.Barkley,
D.Johnson,
and
S.S.Taylor
(2003).
Endogenous tryptophan residues of cAPK regulatory subunit type IIbeta reveal local variations in environments and dynamics.
|
| |
Proteins, 51,
552-561.
|
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|
|
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|
|
K.M.Zawadzki,
Y.Hamuro,
J.S.Kim,
S.Garrod,
D.D.Stranz,
S.S.Taylor,
and
V.L.Woods
(2003).
Dissecting interdomain communication within cAPK regulatory subunit type IIbeta using enhanced amide hydrogen/deuterium exchange mass spectrometry (DXMS).
|
| |
Protein Sci, 12,
1980-1990.
|
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K.Matulef,
and
W.N.Zagotta
(2003).
Cyclic nucleotide-gated ion channels.
|
| |
Annu Rev Cell Dev Biol, 19,
23-44.
|
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|
|
M.E.Wall,
S.H.Francis,
J.D.Corbin,
K.Grimes,
R.Richie-Jannetta,
J.Kotera,
B.A.Macdonald,
R.R.Gibson,
and
J.Trewhella
(2003).
Mechanisms associated with cGMP binding and activation of cGMP-dependent protein kinase.
|
| |
Proc Natl Acad Sci U S A, 100,
2380-2385.
|
|
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|
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|
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M.Punta,
A.Cavalli,
V.Torre,
and
P.Carloni
(2003).
Molecular modeling studies on CNG channel from bovine retinal rod: a structural model of the cyclic nucleotide-binding domain.
|
| |
Proteins, 52,
332-338.
|
|
|
|
|
|
|
W.N.Zagotta,
N.B.Olivier,
K.D.Black,
E.C.Young,
R.Olson,
and
E.Gouaux
(2003).
Structural basis for modulation and agonist specificity of HCN pacemaker channels.
|
| |
Nature, 425,
200-205.
|
|
|
PDB codes:
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J.J.Michel,
and
J.D.Scott
(2002).
AKAP mediated signal transduction.
|
| |
Annu Rev Pharmacol Toxicol, 42,
235-257.
|
|
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|
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|
|
J.M.Enserink,
A.E.Christensen,
J.de Rooij,
M.van Triest,
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Where a reference describes a PDB structure, the PDB
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