PDBsum entry 3cqw

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Transferase PDB id
Protein chain
319 a.a. *
Waters ×143
* Residue conservation analysis
PDB id:
Name: Transferase
Title: Crystal structure of akt-1 complexed with substrate peptide and inhibitor
Structure: Rac-alpha serine/threonine-protein kinase. Chain: a. Fragment: kinase and agc-kinasE C-terminal domains. Synonym: rac-pk-alpha, protein kinase b, pkb, c-akt. Engineered: yes. Mutation: yes. Glycogen synthase kinase-3 beta. Chain: c. Fragment: residues 3-12.
Source: Homo sapiens. Human. Gene: akt1, pkb, rac. Expressed in: spodoptera frugiperda. Synthetic: yes. Other_details: the peptide is naturally found in homo sapiens.
2.00Å     R-factor:   0.203     R-free:   0.257
Authors: J.Pandit
Key ref: B.Lippa et al. (2008). Synthesis and structure based optimization of novel Akt inhibitors. Bioorg Med Chem Lett, 18, 3359-3363. PubMed id: 18456494 DOI: 10.1016/j.bmcl.2008.04.034
03-Apr-08     Release date:   27-May-08    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
P31749  (AKT1_HUMAN) -  RAC-alpha serine/threonine-protein kinase
480 a.a.
319 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 3 residue positions (black crosses)

 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
 Gene Ontology (GO) functional annotation 
  GO annot!
  Biological process     protein phosphorylation   1 term 
  Biochemical function     transferase activity, transferring phosphorus-containing groups     4 terms  


DOI no: 10.1016/j.bmcl.2008.04.034 Bioorg Med Chem Lett 18:3359-3363 (2008)
PubMed id: 18456494  
Synthesis and structure based optimization of novel Akt inhibitors.
B.Lippa, G.Pan, M.Corbett, C.Li, G.S.Kauffman, J.Pandit, S.Robinson, L.Wei, E.Kozina, E.S.Marr, G.Borzillo, E.Knauth, E.G.Barbacci-Tobin, P.Vincent, M.Troutman, D.Baker, F.Rajamohan, S.Kakar, T.Clark, J.Morris.
Based on a high throughput screening hit, pyrrolopyrimidine inhibitors of the Akt kinase are explored. X-ray co-crystal structures of two lead series results in the understanding of key binding interactions, the design of new lead series, and enhanced potency. The syntheses of these series and their biological activities are described. Spiroindoline 13j is found to have an Akt1 kinase IC(50) of 2.4+/-0.6 nM, Akt cell potency of 50+/-19 nM, and provides 68% inhibition of tumor growth in a mouse xenograft model (50 mg/kg, qd, po).

Literature references that cite this PDB file's key reference

  PubMed id Reference
21420856 R.Xu, A.Banka, J.F.Blake, I.S.Mitchell, E.M.Wallace, J.R.Bencsik, N.C.Kallan, K.L.Spencer, S.L.Gloor, M.Martinson, T.Risom, S.D.Gross, T.H.Morales, W.I.Wu, G.P.Vigers, B.J.Brandhuber, and N.J.Skelton (2011).
Discovery of spirocyclic sulfonamides as potent Akt inhibitors with exquisite selectivity against PKA.
  Bioorg Med Chem Lett, 21, 2335-2340.
PDB code: 3qkm
20694263 A.Del Rio, A.J.Barbosa, F.Caporuscio, and G.F.Mangiatordi (2010).
CoCoCo: a free suite of multiconformational chemical databases for high-throughput virtual screening purposes.
  Mol Biosyst, 6, 2122-2128.  
20151677 T.McHardy, J.J.Caldwell, K.M.Cheung, L.J.Hunter, K.Taylor, M.Rowlands, R.Ruddle, A.Henley, Haven Brandon, M.Valenti, T.G.Davies, L.Fazal, L.Seavers, F.I.Raynaud, S.A.Eccles, G.W.Aherne, M.D.Garrett, and I.Collins (2010).
Discovery of 4-amino-1-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidine-4-carboxamides as selective, orally active inhibitors of protein kinase B (Akt).
  J Med Chem, 53, 2239-2249.
PDB codes: 2x37 2x39 2xh5
20886116 W.I.Wu, W.C.Voegtli, H.L.Sturgis, F.P.Dizon, G.P.Vigers, and B.J.Brandhuber (2010).
Crystal structure of human AKT1 with an allosteric inhibitor reveals a new mode of kinase inhibition.
  PLoS One, 5, e12913.
PDB code: 3o96
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