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Transferase PDB id
2hwn
Jmol
Contents
Protein chains
39 a.a. *
45 a.a. *
40 a.a. *
19 a.a. *
20 a.a. *
Ligands
GOL
Waters ×211
* Residue conservation analysis
PDB id:
2hwn
Name: Transferase
Title: Crystal structure of rii alpha dimerization/docking domain o bound to the d-akap2 peptide
Structure: Camp-dependent protein kinase type ii-alpha regul subunit. Chain: a, b, c, d. Fragment: dimerization/docking domain, residues 0-44. Engineered: yes. A kinase binding peptide. Chain: e, f. Engineered: yes
Source: Rattus norvegicus. Norway rat. Organism_taxid: 10116. Gene: prkar2a. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008. Synthetic: yes
Biol. unit: Trimer (from PQS)
Resolution:
1.60Å     R-factor:   0.208     R-free:   0.239
Authors: F.Kinderman,C.Kim
Key ref:
F.S.Kinderman et al. (2006). A dynamic mechanism for AKAP binding to RII isoforms of cAMP-dependent protein kinase. Mol Cell, 24, 397-408. PubMed id: 17081990 DOI: 10.1016/j.molcel.2006.09.015
Date:
01-Aug-06     Release date:   21-Nov-06    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P12368  (KAP2_RAT) -  cAMP-dependent protein kinase type II-alpha regulatory subunit
Seq:
Struc: 		401 a.a.
39 a.a.
Protein chains
Pfam   ArchSchema ?
P12368  (KAP2_RAT) -  cAMP-dependent protein kinase type II-alpha regulatory subunit
Seq:
Struc: 		401 a.a.
45 a.a.
Protein chain
Pfam   ArchSchema ?
P12368  (KAP2_RAT) -  cAMP-dependent protein kinase type II-alpha regulatory subunit
Seq:
Struc: 		401 a.a.
40 a.a.
Protein chain
No UniProt id for this chain
Protein chain
No UniProt id for this chain
Key:    PfamA domain  Secondary structure  CATH domain

 Gene Ontology (GO) functional annotation 
  GO annot!
  Biological process     signal transduction   1 term 
  Biochemical function     cAMP-dependent protein kinase regulator activity     1 term  

 

 
DOI no: 10.1016/j.molcel.2006.09.015 Mol Cell 24:397-408 (2006)
PubMed id: 17081990  
 
 
A dynamic mechanism for AKAP binding to RII isoforms of cAMP-dependent protein kinase.
F.S.Kinderman, C.Kim, S.von Daake, Y.Ma, B.Q.Pham, G.Spraggon, N.H.Xuong, P.A.Jennings, S.S.Taylor.
 
  ABSTRACT  
 
A kinase-anchoring proteins (AKAPs) target PKA to specific microdomains by using an amphipathic helix that docks to N-terminal dimerization and docking (D/D) domains of PKA regulatory (R) subunits. To understand specificity, we solved the crystal structure of the helical motif from D-AKAP2, a dual-specific AKAP, bound to the RIIalpha D/D domain. The 1.6 Angstrom structure reveals how this dynamic, hydrophobic docking site is assembled. A stable, hydrophobic docking groove is formed by the helical interface of two RIIalpha protomers. The flexible N terminus of one protomer is then recruited to the site, anchored to the peptide through two essential isoleucines. The other N terminus is disordered. This asymmetry provides greater possibilities for AKAP docking. Although there is strong discrimination against RIalpha in the N terminus of the AKAP helix, the hydrophobic groove discriminates against RIIalpha. RIalpha, with a cavity in the groove, can accept a bulky tryptophan, whereas RIIalpha requires valine.
 
  Selected figure(s)  
 
Figure 2.
Figure 2. High-Resolution Crystal Structure Depicts RIIα D/D Domain Complexed with the D-AKAP2 Peptide 		Figure 3.
Figure 3. Complementary Hydrophobic Surfaces on RIIα D/D Domain and D-AKAP2 Mediate a Tight Interaction between Helices
 
  The above figures are reprinted by permission from Cell Press: Mol Cell (2006, 24, 397-408) copyright 2006.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21177871 F.Christian, M.Szaszák, S.Friedl, S.Drewianka, D.Lorenz, A.Goncalves, J.Furkert, C.Vargas, P.Schmieder, F.Götz, K.Zühlke, M.Moutty, H.Göttert, M.Joshi, B.Reif, H.Haase, I.Morano, S.Grossmann, A.Klukovits, J.Verli, R.Gáspár, C.Noack, M.Bergmann, R.Kass, K.Hampel, D.Kashin, H.G.Genieser, F.W.Herberg, D.Willoughby, D.M.Cooper, G.S.Baillie, M.D.Houslay, J.P.von Kries, B.Zimmermann, W.Rosenthal, and E.Klussmann (2011).
Small molecule AKAP-protein kinase A (PKA) interaction disruptors that activate PKA interfere with compartmentalized cAMP signaling in cardiac myocytes.
  J Biol Chem, 286, 9079-9096.  
21643460 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.
  Int J Mass Spectrom, 302, 44-52.  
21464287 M.G.Gold, F.Stengel, P.J.Nygren, C.R.Weisbrod, J.E.Bruce, C.V.Robinson, D.Barford, and J.D.Scott (2011).
Architecture and dynamics of an A-kinase anchoring protein 79 (AKAP79) signaling complex.
  Proc Natl Acad Sci U S A, 108, 6426-6431.  
21256157 R.Eglen, and T.Reisine (2011).
Drug discovery and the human kinome: recent trends.
  Pharmacol Ther, 130, 144-156.  
21115539 W.A.McLaughlin, T.Hou, S.S.Taylor, and W.Wang (2011).
The identification of novel cyclic AMP-dependent protein kinase anchoring proteins using bioinformatic filters and peptide arrays.
  Protein Eng Des Sel, 24, 333-339.  
20358582 A.Horvath, J.Bertherat, L.Groussin, M.Guillaud-Bataille, K.Tsang, L.Cazabat, R.Libé, E.Remmers, F.René-Corail, F.R.Faucz, E.Clauser, A.Calender, X.Bertagna, J.A.Carney, and C.A.Stratakis (2010).
Mutations and polymorphisms in the gene encoding regulatory subunit type 1-alpha of protein kinase A (PRKAR1A): an update.
  Hum Mutat, 31, 369-379.  
20668708 B.Xia, A.Joubert, B.Groves, K.Vo, D.Ashraf, D.Djavaherian, J.Awe, Y.Xiong, J.Cherfils, and D.Ma (2010).
Modulation of cell adhesion and migration by the histone methyltransferase subunit mDpy-30 and its interacting proteins.
  PLoS One, 5, e11771.  
20007971 C.Hundsrucker, P.Skroblin, F.Christian, H.M.Zenn, V.Popara, M.Joshi, J.Eichhorst, B.Wiesner, F.W.Herberg, B.Reif, W.Rosenthal, and E.Klussmann (2010).
Glycogen synthase kinase 3beta interaction protein functions as an A-kinase anchoring protein.
  J Biol Chem, 285, 5507-5521.  
20394097 D.Kovanich, M.A.van der Heyden, T.T.Aye, T.A.van Veen, A.J.Heck, and A.Scholten (2010).
Sphingosine kinase interacting protein is an A-kinase anchoring protein specific for type I cAMP-dependent protein kinase.
  Chembiochem, 11, 963-971.  
20368369 E.J.Welch, B.W.Jones, and J.D.Scott (2010).
Networking with AKAPs: context-dependent regulation of anchored enzymes.
  Mol Interv, 10, 86-97.  
20159461 G.N.Sarma, F.S.Kinderman, C.Kim, S.von Daake, L.Chen, B.C.Wang, and S.S.Taylor (2010).
Structure of D-AKAP2:PKA RI complex: insights into AKAP specificity and selectivity.
  Structure, 18, 155-166.
PDB codes: 3im3 3im4
20883492 J.S.Logue, and J.D.Scott (2010).
Organizing signal transduction through A-kinase anchoring proteins (AKAPs).
  FEBS J, 277, 4370-4375.  
19912228 M.Grandoch, S.S.Roscioni, and M.Schmidt (2010).
The role of Epac proteins, novel cAMP mediators, in the regulation of immune, lung and neuronal function.
  Br J Pharmacol, 159, 265-284.  
19897479 P.F.South, I.M.Fingerman, D.P.Mersman, H.N.Du, and S.D.Briggs (2010).
A conserved interaction between the SDI domain of Bre2 and the Dpy-30 domain of Sdc1 is required for histone methylation and gene expression.
  J Biol Chem, 285, 595-607.  
19715558 E.A.Torheim, E.Jarnaess, B.Lygren, and K.Taskén (2009).
Design of proteolytically stable RI-anchoring disruptor peptidomimetics for in vivo studies of anchored type I protein kinase A-mediated signalling.
  Biochem J, 424, 69-78.  
19840947 E.Jarnaess, A.J.Stokka, A.K.Kvissel, B.S.Skålhegg, K.M.Torgersen, J.D.Scott, C.R.Carlson, and K.Taskén (2009).
Splicing factor arginine/serine-rich 17A (SFRS17A) is an A-kinase anchoring protein that targets protein kinase A to splicing factor compartments.
  J Biol Chem, 284, 35154-35164.  
19965465 J.D.Scott, and T.Pawson (2009).
Cell Signaling in Space and Time: Where Proteins Come Together and When They're Apart.
  Science, 326, 1220-1224.  
19726669 J.R.Burgoyne, and P.Eaton (2009).
Transnitrosylating nitric oxide species directly activate type I protein kinase A, providing a novel adenylate cyclase-independent cross-talk to beta-adrenergic-like signaling.
  J Biol Chem, 284, 29260-29268.  
19364910 J.R.Mauban, M.O'Donnell, S.Warrier, S.Manni, and M.Bond (2009).
AKAP-scaffolding proteins and regulation of cardiac physiology.
  Physiology (Bethesda), 24, 78-87.  
19696020 L.Baisamy, S.Cavin, N.Jurisch, and D.Diviani (2009).
The ubiquitin-like protein LC3 regulates the Rho-GEF activity of AKAP-Lbc.
  J Biol Chem, 284, 28232-28242.  
19371331 M.Zaccolo (2009).
cAMP signal transduction in the heart: understanding spatial control for the development of novel therapeutic strategies.
  Br J Pharmacol, 158, 50-60.  
19536823 R.L.Rivard, M.Birger, K.J.Gaston, and A.K.Howe (2009).
AKAP-independent localization of type-II protein kinase A to dynamic actin microspikes.
  Cell Motil Cytoskeleton, 66, 693-709.  
19119138 T.T.Aye, S.Mohammed, H.W.van den Toorn, T.A.van Veen, M.A.van der Heyden, A.Scholten, and A.J.Heck (2009).
Selectivity in enrichment of cAMP-dependent protein kinase regulatory subunits type I and type II and their interactors using modified cAMP affinity resins.
  Mol Cell Proteomics, 8, 1016-1028.  
18625701 A.Islam, H.Jones, T.Hiroi, J.Lam, J.Zhang, J.Moss, M.Vaughan, and S.J.Levine (2008).
cAMP-dependent protein kinase A (PKA) signaling induces TNFR1 exosome-like vesicle release via anchoring of PKA regulatory subunit RIIbeta to BIG2.
  J Biol Chem, 283, 25364-25371.  
18613762 B.Lygren, and K.Taskén (2008).
The potential use of AKAP18delta as a drug target in heart failure patients.
  Expert Opin Biol Ther, 8, 1099-1108.  
18495919 C.E.Chang, W.A.McLaughlin, R.Baron, W.Wang, and J.A.McCammon (2008).
Entropic contributions and the influence of the hydrophobic environment in promiscuous protein-protein association.
  Proc Natl Acad Sci U S A, 105, 7456-7461.  
18824551 E.Jarnaess, A.Ruppelt, A.J.Stokka, B.Lygren, J.D.Scott, and K.Taskén (2008).
Dual specificity A-kinase anchoring proteins (AKAPs) contain an additional binding region that enhances targeting of protein kinase A type I.
  J Biol Chem, 283, 33708-33718.  
18619997 M.S.Cortese, V.N.Uversky, and A.K.Dunker (2008).
Intrinsic disorder in scaffold proteins: getting more from less.
  Prog Biophys Mol Biol, 98, 85.  
  17996741 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.
  Biochim Biophys Acta, 1784, 16-26.  
17827149 A.S.Goehring, B.S.Pedroja, S.A.Hinke, L.K.Langeberg, and J.D.Scott (2007).
MyRIP anchors protein kinase A to the exocyst complex.
  J Biol Chem, 282, 33155-33167.  
17889648 C.Kim, C.Y.Cheng, S.A.Saldanha, and S.S.Taylor (2007).
PKA-I holoenzyme structure reveals a mechanism for cAMP-dependent activation.
  Cell, 130, 1032-1043.
PDB code: 2qcs
17317140 D.L.Beene, and J.D.Scott (2007).
A-kinase anchoring proteins take shape.
  Curr Opin Cell Biol, 19, 192-198.  
17612487 T.Dohi, F.Xia, and D.C.Altieri (2007).
Compartmentalized phosphorylation of IAP by protein kinase A regulates cytoprotection.
  Mol Cell, 27, 17-28.  
17084073 M.G.Gold, D.Barford, and D.Komander (2006).
Lining the pockets of kinases and phosphatases.
  Curr Opin Struct Biol, 16, 693-701.  
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.