PDBsum entry: 3dpd

Transferase

PDB id: 3dpd

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

Protein chain

P48736  (PK3CG_HUMAN) -  Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit gamma isoform

Seq: 1102 a.a.

Struc: 846 a.a.*

* 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.
• 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
• Enzyme class 3: E.C.2.7.11.1 - Non-specific serine/threonine protein kinase.
• Reaction: ATP + a protein = ADP + a 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 

• Cellular component: phosphatidylinositol 3-kinase complex (1 term)
• Biological process: phosphatidylinositol-mediated signaling (2 terms)
• Biochemical function: binding (6 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.