PDBsum entry: 1rgs

Kinase

PDB-id

1rgs

Contents

Description

Header details

Protein chain

Ligands

CMP ×2

* Residue conservation analysis

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PDB id:

1rgs

Name:

Kinase

Title:

Regulatory subunit of camp dependent protein kinase

Structure:

Camp dependent protein kinase. Chain: a. Fragment: regulatory subunit. Synonym: ri(alpha). Engineered: yes. Mutation: yes

Source:

Bos taurus. Cattle. Organism_taxid: 9913. Gene: bovine skeleton muscle. Expressed in: escherichia coli. Expression_system_taxid: 562.

UniProt:

P00514 (KAP0_BOVIN)

Seq:

Struc:

Seq:

380 a.a.

Struc:

264 a.a.

Key:		PfamA domain
		Secondary structure			CATH domain

Resolution:

2.80Å

R-factor:

0.217

Authors:

Y.Su,W.R.G.Dostmann,F.W.Herberg,K.Durick,N.-H.Xuong,L.Ten Eyck,S.S.Taylor,K.I.Varughese

Key ref:

Y.Su et al. (1995). Regulatory subunit of protein kinase A: structure of deletion mutant with cAMP binding domains.. Science, 269, 807-813. [PubMed id: 7638597] [DOI: 10.1126/science.7638597]

Date:

21-Jun-95

Release date:

07-Dec-96

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Key reference

DOI no: 10.1126/science.7638597 Science 269:807-813 (1995)

PubMed id: 7638597

Regulatory subunit of protein kinase A: structure of deletion mutant with cAMP binding domains.

Y.Su, W.R.Dostmann, F.W.Herberg, K.Durick, N.H.Xuong, L.Ten Eyck, S.S.Taylor, K.I.Varughese.

ABSTRACT

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.

Literature references that cite this PDB file's key reference

PubMed id Reference

19063708 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.

19465888 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.

EMBO Rep, 10, 729-735.

PDB code: 2k0g

18404204 A.P.Kornev, S.S.Taylor, and L.F.Ten Eyck (2008).
A generalized allosteric mechanism for cis-regulated cyclic nucleotide binding domains.

PLoS Comput Biol, 4, e1000056.

18426879 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.

Infect Immun, 76, 3075-3085.

18660803 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.

Nature, 455, 124-127.

PDB code: 3cf6

18338824 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.

Proteomics, 8, 1212-1220.

18604457 X.Cheng, Z.Ji, T.Tsalkova, and F.Mei (2008).
Epac and PKA: a tale of two intracellular cAMP receptors.

Acta Biochim Biophys Sin (Shanghai), 40, 651-662.

17403045 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.

FEBS J, 274, 2274-2286.

17261079 D.Moll, S.Schweinsberg, C.Hammann, and F.W.Herberg (2007).
Comparative thermodynamic analysis of cyclic nucleotide binding to protein kinase A.

Biol Chem, 388, 163-172.

17337635 E.M.Rubenstein, and M.C.Schmidt (2007).
Mechanisms regulating the protein kinases of Saccharomyces cerevisiae.

Eukaryot Cell, 6, 571-583.

17183361 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.

17586635 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.

J Bacteriol, 189, 6487-6489.

17255938 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.

17932298 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.

PDB code: 2qvs

17596845 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.

17306374 M.E.Doyle, and J.M.Egan (2007).
Mechanisms of action of glucagon-like peptide 1 in the pancreas.

Pharmacol Ther, 113, 546-593.

18076763 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.

17182741 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.

16522806 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.

PDB code: 1xcr

16322564 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.

16452984 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.

Nature, 439, 625-628.

PDB code: 2byv

16625363 J.Trewhella (2006).
Structural themes and variations in protein kinase A as seen by small-angle scattering and neutron contrast variation.

Eur Biophys J, 35, 585-589.

16460277 K.B.Craven, and W.N.Zagotta (2006).
CNG and HCN channels: two peas, one pod.

Annu Rev Physiol, 68, 375-401.

16500960 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.

16207083 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.

15644130 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.

15981246 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.

15618393 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.

16177794 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.

15727824 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.

14722619 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.

14583592 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.

PDB code: 1pvk

12469113 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: 1o7f

14506476 J.L.Bos (2003).
Epac: a new cAMP target and new avenues in cAMP research.

Nat Rev Mol Cell Biol, 4, 733-738.

12784214 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.

12930997 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.

14570562 K.Matulef, and W.N.Zagotta (2003).
Cyclic nucleotide-gated ion channels.

Annu Rev Cell Dev Biol, 19, 23-44.

12591946 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.

12866047 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.

12968185 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: 1q3e 1q43 1q5o

11807172 J.J.Michel, and J.D.Scott (2002).
AKAP mediated signal transduction.

Annu Rev Pharmacol Toxicol, 42, 235-257.

12402047 J.M.Enserink, A.E.Christensen, J.de Rooij, M.van Triest, F.Schwede, H.G.Genieser, S.O.Døskeland, J.L.Blank, and J.L.Bos (2002).
A novel Epac-specific cAMP analogue demonstrates independent regulation of Rap1 and ERK.

Nat Cell Biol, 4, 901-906.

12011437 J.M.Goldberg, L.Bosgraaf, P.J.Van Haastert, and J.L.Smith (2002).
Identification of four candidate cGMP targets in Dictyostelium.

Proc Natl Acad Sci U S A, 99, 6749-6754.

12048242 M.C.Trudeau, and W.N.Zagotta (2002).
Mechanism of calcium/calmodulin inhibition of rod cyclic nucleotide-gated channels.

Proc Natl Acad Sci U S A, 99, 8424-8429.

12429831 M.E.Meima, R.M.Biondi, and P.Schaap (2002).
Identification of a novel type of cGMP phosphodiesterase that is defective in the chemotactic stmF mutants.

Mol Biol Cell, 13, 3870-3877.

12496096 M.Mazzolini, M.Punta, and V.Torre (2002).
Movement of the C-helix during the gating of cyclic nucleotide-gated channels.

Biophys J, 83, 3283-3295.

11696610 E.C.Young, D.M.Sciubba, and S.A.Siegelbaum (2001).
Efficient coupling of ligand binding to channel opening by the binding domain of a modulatory (beta) subunit of the olfactory cyclic nucleotide-gated channel.

J Gen Physiol, 118, 523-546.

11325927 J.Kwak, L.A.McCue, K.Trczianka, and K.E.Kendrick (2001).
Identification and characterization of a developmentally regulated protein, EshA, required for sporogenic hyphal branches in Streptomyces griseus.

J Bacteriol, 183, 3004-3015.

11331358 S.Chen, J.Wang, and S.A.Siegelbaum (2001).
Properties of hyperpolarization-activated pacemaker current defined by coassembly of HCN1 and HCN2 subunits and basal modulation by cyclic nucleotide.

J Gen Physiol, 117, 491-504.

11733015 T.Shalaby, M.Liniger, and T.Seebeck (2001).
The regulatory subunit of a cGMP-regulated protein kinase A of Trypanosoma brucei.

Eur J Biochem, 268, 6197-6206.

11181956 U.B.Kaupp, and R.Seifert (2001).
Molecular diversity of pacemaker ion channels.

Annu Rev Physiol, 63, 235-257.

10801316 D.A.Leon, J.M.Canaves, and S.S.Taylor (2000).
Probing the multidomain structure of the type I regulatory subunit of cAMP-dependent protein kinase using mutational analysis: role and environment of endogenous tryptophans.

Biochemistry, 39, 5662-5671.

10944347 D.E.Danley, M.E.Haggan, D.Cunningham, K.F.Fennell, T.A.Pauly, and P.K.LeMotte (2000).
A crystallizable form of RIIbeta regulatory domain obtained by limited proteolysis.

Acta Crystallogr D Biol Crystallogr, 56, 1038-1041.

11112551 F.Li, M.Gangal, J.M.Jones, J.Deich, K.E.Lovett, S.S.Taylor, and D.A.Johnson (2000).
Consequences of cAMP and catalytic-subunit binding on the flexibility of the A-kinase regulatory subunit.

Biochemistry, 39, 15626-15632.

10913291 F.Schwede, A.Christensen, S.Liauw, T.Hippe, R.Kopperud, B.Jastorff, and S.O.Døskeland (2000).
8-Substituted cAMP analogues reveal marked differences in adaptability, hydrogen bonding, and charge accommodation between homologous binding sites (AI/AII and BI/BII) in cAMP kinase I and II.

Biochemistry, 39, 8803-8812.

10777729 M.S.Shapiro, and W.N.Zagotta (2000).
Structural basis for ligand selectivity of heteromeric olfactory cyclic nucleotide-gated channels.

Biophys J, 78, 2307-2320.

10919868 S.E.Gordon (2000).
"Light" reading: targeting tryptophans in cyclic nucleotide-gated channels.

J Gen Physiol, 116, 223-225.

11206066 W.W.Muhonen, and J.B.Shabb (2000).
Resonant mirror biosensor analysis of type Ialpha cAMP-dependent protein kinase B domain--cyclic nucleotide interactions.

Protein Sci, 9, 2446-2456.

11032796 Y.S.Ho, L.M.Burden, and J.H.Hurley (2000).
Structure of the GAF domain, a ubiquitous signaling motif and a new class of cyclic GMP receptor.

EMBO J, 19, 5288-5299.

PDB codes: 1f5m 1fl4

9874685 P.Paoletti, E.C.Young, and S.A.Siegelbaum (1999).
C-Linker of cyclic nucleotide-gated channels controls coupling of ligand binding to channel gating.

J Gen Physiol, 113, 17-34.

9860838 S.P.Scott, and J.C.Tanaka (1998).
Three residues predicted by molecular modeling to interact with the purine moiety alter ligand binding and channel gating in cyclic nucleotide-gated channels.

Biochemistry, 37, 17239-17252.

9009262 K.A.Watson, R.Schinzel, D.Palm, and L.N.Johnson (1997).
The crystal structure of Escherichia coli maltodextrin phosphorylase provides an explanation for the activity without control in this basic archetype of a phosphorylase.

EMBO J, 16, 1.

9300482 R.M.Gibson, Y.Ji-Buechler, and S.S.Taylor (1997).
Identification of electrostatic interaction sites between the regulatory and catalytic subunits of cyclic AMP-dependent protein kinase.

Protein Sci, 6, 1825-1834.

8744304 M.D.Varnum, and W.N.Zagotta (1996).
Subunit interactions in the activation of cyclic nucleotide-gated ion channels.

Biophys J, 70, 2667-2679.

8672432 S.E.Gordon, J.C.Oakley, M.D.Varnum, and W.N.Zagotta (1996).
Altered ligand specificity by protonation in the ligand binding domain of cyclic nucleotide-gated channels.

Biochemistry, 35, 3994-4001.

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 code is shown on the right.