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PDBsum entry 3prz

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protein ligands links
Transferase/transferase inhibitor PDB id
3prz
Jmol
Contents
Protein chain
844 a.a. *
Ligands
3RZ
* Residue conservation analysis
PDB id:
3prz
Name: Transferase/transferase inhibitor
Title: Quinazolines with intra-molecular hydrogen bonding scaffold pi3k/mtor dual inhibitors.
Structure: Phosphatidylinositol-4,5-bisphosphate 3-kinase ca subunit gamma isoform. Chain: a. Fragment: unp residues 144-1102. Synonym: ptdins-3-kinase subunit gamma, pi3-kinase subunit pi3k-gamma, phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit gamma, ptdins-3-kinase subunit p110-gamma pi3k. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: pik3cg. Expressed in: spodoptera frugiperda. Expression_system_taxid: 7108
Resolution:
2.60Å     R-factor:   0.251     R-free:   0.281
Authors: D.R.Knighton,S.E.Greasley,C.M.-L.Rodgers
Key ref: K.K.Liu et al. (2011). Quinazolines with intra-molecular hydrogen bonding scaffold (iMHBS) as PI3K/mTOR dual inhibitors. Bioorg Med Chem Lett, 21, 1270-1274. PubMed id: 21269826 DOI: 10.1016/j.bmcl.2010.12.026
Date:
30-Nov-10     Release date:   09-Feb-11    
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.
844 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: 10.1016/j.bmcl.2010.12.026 Bioorg Med Chem Lett 21:1270-1274 (2011)
PubMed id: 21269826  
 
 
Quinazolines with intra-molecular hydrogen bonding scaffold (iMHBS) as PI3K/mTOR dual inhibitors.
K.K.Liu, X.Huang, S.Bagrodia, J.H.Chen, S.Greasley, H.Cheng, S.Sun, D.Knighton, C.Rodgers, K.Rafidi, A.Zou, J.Xiao, S.Yan.
 
  ABSTRACT  
 
Intra-molecular hydrogen bonding was introduced to the quinazoline motif to form a pseudo ring (intra-molecular H-bond scaffold, iMHBS) to mimic our previous published core structures, pyrido[2.3-D]pyrimidin-7-one and pteridinone, as PI3K/mTOR dual inhibitors. This design results in potent PI3K/mTOR dual inhibitors and the purposed intra-molecular hydrogen bonding structure is well supported by co-crystal structure in PI3Kγ enzyme. In addition, a novel synthetic route was developed for these analogs.