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PDBsum entry 3dpd

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protein ligands links
Transferase PDB id
3dpd
Jmol
Contents
Protein chain
846 a.a. *
Ligands
41A
* Residue conservation analysis
PDB id:
3dpd
Name: Transferase
Title: Achieving multi-isoform pi3k inhibition in a series of substituted 3,4-dihydro-2h-benzo[1,4]oxazines
Structure: Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit gamma isoform. Chain: a. Fragment: residues 144-1102. Synonym: pi3-kinase p110 subunit gamma, ptdins-3-kinase subunit p110, pi3kgamma, pi3k, p120-pi3k. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: pik3cg. Expressed in: spodoptera frugiperda. Expression_system_taxid: 7108.
Resolution:
2.85Å     R-factor:   0.242     R-free:   0.318
Authors: T.A.Ceska
Key ref: B.Perry et al. (2008). Achieving multi-isoform PI3K inhibition in a series of substituted 3,4-dihydro-2H-benzo[1,4]oxazines. Bioorg Med Chem Lett, 18, 4700-4704. PubMed id: 18644721 DOI: 10.1016/j.bmcl.2008.06.104
Date:
08-Jul-08     Release date:   26-Aug-08    
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.
846 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 2 residue positions (black crosses)

 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: 10.1016/j.bmcl.2008.06.104 Bioorg Med Chem Lett 18:4700-4704 (2008)
PubMed id: 18644721  
 
 
Achieving multi-isoform PI3K inhibition in a series of substituted 3,4-dihydro-2H-benzo[1,4]oxazines.
B.Perry, R.Alexander, G.Bennett, G.Buckley, T.Ceska, T.Crabbe, V.Dale, L.Gowers, H.Horsley, L.James, K.Jenkins, K.Crépy, C.Kulisa, H.Lightfoot, C.Lock, S.Mack, T.Morgan, A.L.Nicolas, W.Pitt, V.Sabin, S.Wright.
 
  ABSTRACT  
 
The SAR and pharmacokinetic profiles of a series of multi-isoform PI3K inhibitors based on a 3,4-dihydro-2H-benzo[1,4]oxazine scaffold are disclosed.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
19962457 S.B.Gabelli, D.Mandelker, O.Schmidt-Kittler, B.Vogelstein, and L.M.Amzel (2010).
Somatic mutations in PI3Kalpha: structural basis for enzyme activation and drug design.
  Biochim Biophys Acta, 1804, 533-540.  
19225663 T.J.Sundstrom, A.C.Anderson, and D.L.Wright (2009).
Inhibitors of phosphoinositide-3-kinase: a structure-based approach to understanding potency and selectivity.
  Org Biomol Chem, 7, 840-850.  
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