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PDBsum entry 4fjy

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protein ligands links
Transferase/inhibitor PDB id
4fjy
Jmol
Contents
Protein chain
839 a.a.
Ligands
SO4 ×3
FJY
Waters ×13
PDB id:
4fjy
Name: Transferase/inhibitor
Title: Crystal structure of pi3k-gamma in complex with quinoline-in inhibitor 24f
Structure: Phosphatidylinositol 4,5-bisphosphate 3-kinase ca subunit gamma isoform. Chain: a. Fragment: catalytic domain, unp residues 144-1102. Synonym: pi3-kinase subunit gamma, pi3k-gamma, pi3kgamma, p kinase subunit gamma, phosphatidylinositol 4,5-bisphosphate 110 kda catalytic subunit gamma, ptdins-3-kinase subunit p1 p110gamma, phosphoinositide-3-kinase catalytic gamma polype serine/threonine protein kinase pik3cg, p120-pi3k.
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: pik3cg. Expressed in: spodoptera frugiperda. Expression_system_taxid: 7108. Expression_system_cell_line: sf9.
Resolution:
2.90Å     R-factor:   0.203     R-free:   0.275
Authors: D.A.Whittington,J.Tang,P.Yakowec
Key ref: F.Gonzalez-Lopez de Turiso et al. (2012). Discovery and in vivo evaluation of dual PI3Kβ/δ inhibitors. J Med Chem, 55, 7667-7685. PubMed id: 22876881 DOI: 10.1021/jm300679u
Date:
12-Jun-12     Release date:   24-Oct-12    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P48736  (PK3CG_HUMAN) -  Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform
Seq:
Struc:
 
Seq:
Struc:
 
Seq:
Struc:
1102 a.a.
839 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class 2: E.C.2.7.1.153  - Phosphatidylinositol-4,5-bisphosphate 3-kinase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]

      Pathway:
1-Phosphatidyl-myo-inositol Metabolism
      Reaction: ATP + 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate = ADP + 1-phosphatidyl-1D-myo-inositol 3,4,5-trisphosphate
ATP
+ 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate
= ADP
+ 1-phosphatidyl-1D-myo-inositol 3,4,5-trisphosphate
   Enzyme class 3: E.C.2.7.11.1  - Non-specific serine/threonine protein kinase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: ATP + a protein = ADP + a phosphoprotein
ATP
+ protein
= ADP
+ phosphoprotein
Note, where more than one E.C. class is given (as above), each may correspond to a different protein domain or, in the case of polyprotein precursors, to a different mature protein.
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Biological process     phosphatidylinositol-mediated signaling   2 terms 
  Biochemical function     transferase activity, transferring phosphorus-containing groups     2 terms  

 

 
    reference    
 
 
DOI no: 10.1021/jm300679u J Med Chem 55:7667-7685 (2012)
PubMed id: 22876881  
 
 
Discovery and in vivo evaluation of dual PI3Kβ/δ inhibitors.
F.Gonzalez-Lopez de Turiso, Y.Shin, M.Brown, M.Cardozo, Y.Chen, D.Fong, X.Hao, X.He, K.Henne, Y.L.Hu, M.G.Johnson, T.Kohn, J.Lohman, H.J.McBride, L.R.McGee, J.C.Medina, D.Metz, K.Miner, D.Mohn, V.Pattaropong, J.Seganish, J.L.Simard, S.Wannberg, D.A.Whittington, G.Yu, T.D.Cushing.
 
  ABSTRACT  
 
Structure-based rational design led to the synthesis of a novel series of potent PI3K inhibitors. The optimized pyrrolopyridine analogue 63 was a potent and selective PI3Kβ/δ dual inhibitor that displayed suitable physicochemical properties and pharmacokinetic profile for animal studies. Analogue 63 was found to be efficacious in animal models of inflammation including a keyhole limpet hemocyanin (KLH) study and a collagen-induced arthritis (CIA) disease model of rheumatoid arthritis. These studies highlight the potential therapeutic value of inhibiting both the PI3Kβ and δ isoforms in the treatment of a number of inflammatory diseases.