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PDBsum entry 2gu8
Go to PDB code: 
protein ligands Protein-protein interface(s) links
Signaling protein,transferase/inhibitor PDB id
2gu8

 

 

 

 

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JSmol PyMol  
Contents
Protein chains
337 a.a. *
20 a.a. *
Ligands
796
Waters ×170
* Residue conservation analysis
PDB id:
2gu8
Name: Signaling protein,transferase/inhibitor
Title: Discovery of 2-pyrimidyl-5-amidothiophenes as novel and potent inhibitors for akt: synthesis and sar studies
Structure: Camp-dependent protein kinase, alpha-catalytic subunit. Chain: a. Fragment: catalytic subunit. Synonym: pka c-alpha. Engineered: yes. Inhibitor of camp-dependent protein kinase. Chain: c. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 562. Synthetic: yes
Resolution:
2.20Å     R-factor:   0.206     R-free:   0.261
Authors: J.M.Murray
Key ref: X.Lin et al. (2006). Discovery of 2-pyrimidyl-5-amidothiophenes as potent inhibitors for AKT: synthesis and SAR studies. Bioorg Med Chem Lett, 16, 4163-4168. PubMed id: 16765046
Date:
28-Apr-06     Release date:   01-May-07    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P17612  (KAPCA_HUMAN) -  cAMP-dependent protein kinase catalytic subunit alpha from Homo sapiens
Seq:
Struc: 		351 a.a.
337 a.a.*
Protein chain
No UniProt id for this chain
Struc: 20 a.a.
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 9 residue positions (black crosses)

 Enzyme reactions 
   Enzyme class: Chain A: E.C.2.7.11.11  - cAMP-dependent 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    
 
 
Bioorg Med Chem Lett 16:4163-4168 (2006)
PubMed id: 16765046  
 
 
Discovery of 2-pyrimidyl-5-amidothiophenes as potent inhibitors for AKT: synthesis and SAR studies.
X.Lin, J.M.Murray, A.C.Rico, M.X.Wang, D.T.Chu, Y.Zhou, M.Del Rosario, S.Kaufman, S.Ma, E.Fang, K.Crawford, A.B.Jefferson.
 
  ABSTRACT  
 
A series of 2-pyrimidyl-5-amidothiophenes has been synthesized and evaluated for AKT inhibition. SAR studies resulted in potent inhibitors of AKT with IC(50) values as low as single digit nanomolar as represented by compound 2aa. Compound 2aa showed cellular activity including antiproliferation and downstream target modulation. Selectivity profile is described. A co-crystal of 2aa with PKA is determined and discussed.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
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
  19177354 G.T.Lountos, J.E.Tropea, D.Zhang, A.G.Jobson, Y.Pommier, R.H.Shoemaker, and D.S.Waugh (2009).
Crystal structure of checkpoint kinase 2 in complex with NSC 109555, a potent and selective inhibitor.
  Protein Sci, 18, 92.
PDB code: 2w0j
19568781 L.A.Smyth, and I.Collins (2009).
Measuring and interpreting the selectivity of protein kinase inhibitors.
  J Chem Biol, 2, 131-151.  
19075596 J.P.Gustin, D.P.Cosgrove, and B.H.Park (2008).
The PIK3CA gene as a mutated target for cancer therapy.
  Curr Cancer Drug Targets, 8, 733-740.  
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.

 

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