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PDBsum entry 1rl3
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protein ligands Protein-protein interface(s) links
Kinase PDB id
1rl3

 

 

 

 

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JSmol PyMol  
Contents
Protein chains
268 a.a. *
Ligands
PCG ×2
GOL ×3
Waters ×17
* Residue conservation analysis
PDB id:
1rl3
Name: Kinase
Title: Crystal structure of camp-free r1a subunit of pka
Structure: Camp-dependent protein kinase type i-alpha regulatory chain. Chain: a, b. Engineered: yes
Source: Bos taurus. Cattle. Organism_taxid: 9913. Gene: prkar1a. Expressed in: escherichia coli. Expression_system_taxid: 562
Biol. unit: Dimer (from PQS)
Resolution:
2.70Å     R-factor:   0.240     R-free:   0.285
Authors: J.Wu,S.Brown,N.-H.Xuong,S.S.Taylor
Key ref:
J.Wu et al. (2004). RIalpha subunit of PKA: a cAMP-free structure reveals a hydrophobic capping mechanism for docking cAMP into site B. Structure, 12, 1057-1065. PubMed id: 15274925 DOI: 10.1016/j.str.2004.03.022
Date:
24-Nov-03     Release date:   06-Jul-04    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
P00514  (KAP0_BOVIN) -  cAMP-dependent protein kinase type I-alpha regulatory subunit from Bos taurus
Seq:
Struc: 		380 a.a.
268 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 

 
DOI no: 10.1016/j.str.2004.03.022 Structure 12:1057-1065 (2004)
PubMed id: 15274925  
 
 
RIalpha subunit of PKA: a cAMP-free structure reveals a hydrophobic capping mechanism for docking cAMP into site B.
J.Wu, S.Brown, N.H.Xuong, S.S.Taylor.
 
  ABSTRACT  
 
In eukaryotes the primary target for cAMP, a ubiquitous second messenger, is cAMP-dependent protein kinase (PKA). Understanding how binding and release of cAMP changes the cAMP binding domains and then triggers long-range allosteric responses is an important challenge. This conformational switching requires structure solutions of cAMP binding domains in cAMP-bound and cAMP-free states. We describe for the first time a crystal structure of the cAMP binding domains of PKA type Ialpha regulatory subunit where site A is occupied by cGMP and site B is unoccupied. The structure reveals that the carboxyl terminus of domain B serves as a hydrophobic cap, locking the cyclic nucleotide via its adenine ring into the beta-barrel. In the absence of cAMP, the "cap" is released via an extension of the C-terminal helix. This simple hinge mechanism for binding and release of cAMP also provides a mechanism for allosteric communication between sites A and B.
 
  Selected figure(s)  
 
Figure 6.
Figure 6. The Domain Organization and the Functional Sites of RIa Are HighlightedDomain B is in light blue, domain A is dark blue, and the N-terminal segment preceding the domain is in tan. The C helices and PBC motifs in domain A and B are shown in red and orange, respectively.
 
  The above figure is reprinted by permission from Cell Press: Structure (2004, 12, 1057-1065) copyright 2004.  
  Figure was selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
20729090 A.Cukkemane, R.Seifert, and U.B.Kaupp (2011).
Cooperative and uncooperative cyclic-nucleotide-gated ion channels.
  Trends Biochem Sci, 36, 55-64.  
20367611 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.  
19132361 A.V.Nair, C.Anselmi, and M.Mazzolini (2009).
Movements of native C505 during channel gating in CNGA1 channels.
  Eur Biophys J, 38, 465-478.  
19837668 C.Y.Cheng, J.Yang, S.S.Taylor, and D.K.Blumenthal (2009).
Sensing domain dynamics in protein kinase A-I{alpha} complexes by solution X-ray scattering.
  J Biol Chem, 284, 35916-35925.  
19403523 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.
  J Biol Chem, 284, 23682-23696.  
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.  
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.  
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.  
17785454 M.Brock, F.Fan, F.C.Mei, S.Li, C.Gessner, V.L.Woods, and X.Cheng (2007).
Conformational analysis of Epac activation using amide hydrogen/deuterium exchange mass spectrometry.
  J Biol Chem, 282, 32256-32263.  
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.  
16407073 J.Gullingsrud, C.Kim, S.S.Taylor, and J.A.McCammon (2006).
Dynamic binding of PKA regulatory subunit RI alpha.
  Structure, 14, 141-149.  
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.  
17073662 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.  
17176054 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.  
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.  
16109722 D.Vigil, D.K.Blumenthal, S.S.Taylor, and J.Trewhella (2005).
The conformationally dynamic C helix of the RIalpha subunit of protein kinase A mediates isoform-specific domain reorganization upon C subunit binding.
  J Biol Chem, 280, 35521-35527.  
15813735 M.Eiting, G.Hagelüken, W.D.Schubert, and D.W.Heinz (2005).
The mutation G145S in PrfA, a key virulence regulator of Listeria monocytogenes, increases DNA-binding affinity by stabilizing the HTH motif.
  Mol Microbiol, 56, 433-446.
PDB codes: 2beo 2bgc
15550244 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.
PDB codes: 1u12 1vp6
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.

 

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