PDBsum entry 1p6s

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protein links
Transferase PDB id
Protein chain
111 a.a. *
* Residue conservation analysis
PDB id:
Name: Transferase
Title: Solution structure of the pleckstrin homology domain of human protein kinase b beta (pkb/akt)
Structure: Rac-beta serine/threonine protein kinase. Chain: a. Fragment: pleckstrin homology domain (residues 1-111). Synonym: rac-pk-beta, protein kinase akt-2, protein kinase b, beta, pkb beta. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: akt2. Expressed in: escherichia coli bl21. Expression_system_taxid: 511693.
NMR struc: 20 models
Authors: D.Auguin,P.Barthe,M.T.Auge-Senegas,M.H.Stern,M.Noguchi, C.Roumestand
Key ref: D.Auguin et al. (2004). Solution structure and backbone dynamics of the pleckstrin homology domain of the human protein kinase B (PKB/Akt). Interaction with inositol phosphates. J Biomol NMR, 28, 137-155. PubMed id: 14755158
30-Apr-03     Release date:   18-May-04    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
P31751  (AKT2_HUMAN) -  RAC-beta serine/threonine-protein kinase
481 a.a.
111 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.  - Non-specific serine/threonine protein kinase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: ATP + a protein = ADP + a phosphoprotein
+ protein
+ phosphoprotein
Molecule diagrams generated from .mol files obtained from the KEGG ftp site


J Biomol NMR 28:137-155 (2004)
PubMed id: 14755158  
Solution structure and backbone dynamics of the pleckstrin homology domain of the human protein kinase B (PKB/Akt). Interaction with inositol phosphates.
D.Auguin, P.Barthe, M.T.Augé-Sénégas, M.H.Stern, M.Noguchi, C.Roumestand.
The programmed cell death occurs as part of normal mammalian development. The induction of developmental cell death is a highly regulated process and can be suppressed by a variety of extracellular stimuli. Recently, the ability of trophic factors to promote survival have been attributed, at least in part, to the phosphatidylinositide 3'-OH kinase (PI3K)/Protein Kinase B (PKB, also named Akt) cascade. Several targets of the PI3K/PKB signaling pathway have been identified that may underlie the ability of this regulatory cascade to promote cell survival. PKB possesses a N-terminal Pleckstrin Homology (PH) domain that binds specifically and with high affinity to PtIns(3,4,5)P(3) and PtIns(3,4)P(2), the PI3K second messengers. PKB is then recruited to the plasma membrane by virtue of its interaction with 3'-OH phosphatidylinositides and activated. Recent evidence indicates that PKB is active in various types of human cancer; constitutive PKB signaling activation is believed to promote proliferation and increased cell survival, thereby contributing to cancer progression. Thus, it has been shown that induction of PKB activity is augmented by the TCL1/MTCP1 oncoproteins through a physical association requiring the PKB PH domain. Here we present the three-dimensional solution structure of the PH domain of the human protein PKB (isoform beta). PKBbeta-PH is an electrostatically polarized molecule that adopts the same fold and topology as other PH-domains, consisting of a beta-sandwich of seven strands capped on one top by an alpha-helix. The opposite face presents three variable loops that appear poorly defined in the NMR structure. Measurements of (15)N spin relaxation times and heteronuclear (15)N[(1)H]NOEs showed that this poor definition is due to intrinsic flexibility, involving complex motions on different time scales. Chemical shift mapping studies correctly defined the binding site of Ins(1,3,4,5)P(4) (the head group of PtIns(3,4,5)P(3)), as was previously proposed from a crystallographic study. More interestingly, these studies allowed us to define a putative alternative low-affinity binding site for Ins(1,4,5)P(3). The binding of this sugar to PKBbeta-PH might also involve non-specific association that could explain the stabilization of the protein in solution in the presence of Ins(1,4,5)P(3).

Literature references that cite this PDB file's key reference

  PubMed id Reference
21041639 B.Miao, I.Skidan, J.Yang, A.Lugovskoy, M.Reibarkh, K.Long, T.Brazell, K.A.Durugkar, J.Maki, C.V.Ramana, B.Schaffhausen, G.Wagner, V.Torchilin, J.Yuan, and A.Degterev (2010).
Small molecule inhibition of phosphatidylinositol-3,4,5-triphosphate (PIP3) binding to pleckstrin homology domains.
  Proc Natl Acad Sci U S A, 107, 20126-20131.  
20489726 N.Berndt, H.Yang, B.Trinczek, S.Betzi, Z.Zhang, B.Wu, N.J.Lawrence, M.Pellecchia, E.Schönbrunn, J.Q.Cheng, and S.M.Sebti (2010).
The Akt activation inhibitor TCN-P inhibits Akt phosphorylation by binding to the PH domain of Akt and blocking its recruitment to the plasma membrane.
  Cell Death Differ, 17, 1795-1804.  
19446470 B.X.Huang, and H.Y.Kim (2009).
Probing Akt-inhibitor interaction by chemical cross-linking and mass spectrometry.
  J Am Soc Mass Spectrom, 20, 1504-1513.  
19462409 M.Guo, B.X.Huang, and H.Y.Kim (2009).
Conformational changes in Akt1 activation probed by amide hydrogen/deuterium exchange and nano-electrospray ionization mass spectrometry.
  Rapid Commun Mass Spectrom, 23, 1885-1891.  
19568789 V.Calleja, M.Laguerre, and B.Larijani (2009).
3-D structure and dynamics of protein kinase B-new mechanism for the allosteric regulation of an AGC kinase.
  J Chem Biol, 2, 11-25.  
19668332 V.Ropars, G.Despouy, M.H.Stern, S.Benichou, C.Roumestand, and S.T.Arold (2009).
The TCL1A oncoprotein interacts directly with the NF-kappaB inhibitor IkappaB.
  PLoS One, 4, e6567.  
18073205 D.Bessière, C.Lacroix, S.Campagne, V.Ecochard, V.Guillet, L.Mourey, F.Lopez, J.Czaplicki, P.Demange, A.Milon, J.P.Girard, and V.Gervais (2008).
Structure-function analysis of the THAP zinc finger of THAP1, a large C2CH DNA-binding module linked to Rb/E2F pathways.
  J Biol Chem, 283, 4352-4363.
PDB code: 2jtg
18489586 L.A.Alcaraz, M.Del Alamo, M.G.Mateu, and J.L.Neira (2008).
Structural mobility of the monomeric C-terminal domain of the HIV-1 capsid protein.
  FEBS J, 275, 3299-3311.  
18004759 S.O.Yesylevskyy, V.N.Kharkyanen, and A.P.Demchenko (2008).
The blind search for the closed states of hinge-bending proteins.
  Proteins, 71, 831-843.  
17825284 S.Wang, and M.D.Basson (2008).
Identification of functional domains in AKT responsible for distinct roles of AKT isoforms in pressure-stimulated cancer cell adhesion.
  Exp Cell Res, 314, 286-296.  
17580302 B.Dong, C.A.Valencia, and R.Liu (2007).
Ca(2+)/calmodulin directly interacts with the pleckstrin homology domain of AKT1.
  J Biol Chem, 282, 25131-25140.  
17500509 H.Al-Ali, T.J.Ragan, X.Gao, and T.K.Harris (2007).
Reconstitution of modular PDK1 functions on trans-splicing of the regulatory PH and catalytic kinase domains.
  Bioconjug Chem, 18, 1294-1302.  
16877502 S.O.Yesylevskyy, V.N.Kharkyanen, and A.P.Demchenko (2006).
The change of protein intradomain mobility on ligand binding: is it a commonly observed phenomenon?
  Biophys J, 91, 3002-3013.  
16288296 C.C.Kumar, and V.Madison (2005).
AKT crystal structure and AKT-specific inhibitors.
  Oncogene, 24, 7493-7501.  
16041729 X.M.Lu, M.Lu, R.G.Tompkins, and A.J.Fischman (2005).
Site-specific detection of S-nitrosylated PKB alpha/Akt1 from rat soleus muscle using CapLC-Q-TOF(micro) mass spectrometry.
  J Mass Spectrom, 40, 1140-1148.  
15169787 D.Auguin, P.Barthe, C.Royer, M.H.Stern, M.Noguchi, S.T.Arold, and C.Roumestand (2004).
Structural basis for the co-activation of protein kinase B by T-cell leukemia-1 (TCL1) family proto-oncoproteins.
  J Biol Chem, 279, 35890-35902.  
15459205 M.Hiromura, F.Okada, T.Obata, D.Auguin, T.Shibata, C.Roumestand, and M.Noguchi (2004).
Inhibition of Akt kinase activity by a peptide spanning the betaA strand of the proto-oncogene TCL1.
  J Biol Chem, 279, 53407-53418.  
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.