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PDBsum entry 3cqu
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protein ligands links
Transferase PDB id
3cqu

 

 

 

 

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Contents
Protein chain
319 a.a. *
Ligands
GLY-ARG-PRO-ARG-
THR-THR-SER-PHE-
ALA-GLU
CQU
Waters ×192
* Residue conservation analysis
PDB id:
3cqu
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. Organism_taxid: 9606. Gene: akt1, pkb, rac. Expressed in: spodoptera frugiperda. Expression_system_taxid: 7108. Expression_system_cell_line: sf9. Synthetic: yes. Organism_taxid: 9606
Resolution:
2.20Å     R-factor:   0.207     R-free:   0.283
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
Date:
03-Apr-08     Release date:   27-May-08    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P31749  (AKT1_HUMAN) -  RAC-alpha serine/threonine-protein kinase from Homo sapiens
Seq:
Struc: 		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.2.7.11.1  - non-specific serine/threonine protein kinase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction:
1. L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP + H+
2. L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] + ADP + H+
L-seryl-[protein]
 + ATP
 = O-phospho-L-seryl-[protein]
 + ADP
 + H(+)
L-threonyl-[protein]
 + ATP
 = O-phospho-L-threonyl-[protein]
 + ADP
 + H(+)
Molecule diagrams generated from .mol files obtained from the KEGG ftp site

 

 
    reference    
 
 
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.
 
  ABSTRACT  
 
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, A.de 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
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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