PDBsum entry 5swr

Transferase/transferase inhibitor

PDB id: 5swr

Contents

Protein chains

1053 a.a.

252 a.a.

Ligands

718

SAL

Metals

_CL ×2

PDB id:

5swr

Name:

Transferase/transferase inhibitor

Title:

Crystal structure of pi3kalpha in complex with fragments 20 and 26

Structure:

Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform. Chain: a. Synonym: ptdins-3-kinase subunit alpha,phosphatidylinositol 4,5- bisphosphate 3-kinase 110 kda catalytic subunit alpha,p110alpha, phosphoinositide-3-kinase catalytic alpha polypeptide, serine/threonine protein kinase pik3ca. Engineered: yes. Phosphatidylinositol 3-kinase regulatory subunit alpha.

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: pik3ca. Expressed in: spodoptera frugiperda. Expression_system_taxid: 7108. Expression_system_cell_line: sf9. Gene: pik3r1, grb1.

Resolution:

3.31Å R-factor: 0.201 R-free: 0.273

Authors:

S.B.Gabelli,B.Vogelstein,M.S.Miller,L.M.Amzel

Key ref:

M.S.Miller et al. (2017). Identification of allosteric binding sites for PI3Kα oncogenic mutant specific inhibitor design. Bioorg Med Chem Lett, 25, 1481-1486. PubMed id: 28129991 DOI: 10.1016/j.bmc.2017.01.012

Date:

08-Aug-16 Release date: 15-Feb-17

Protein chain

P42336  (PK3CA_HUMAN) -  Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform from Homo sapiens

Seq: 1068 a.a.

Struc: 1053 a.a.

Protein chain

P27986  (P85A_HUMAN) -  Phosphatidylinositol 3-kinase regulatory subunit alpha from Homo sapiens

Seq: 724 a.a.

Struc: 252 a.a.

Enzyme reactions

• Enzyme class 2: Chain A: E.C.2.7.1.137 - phosphatidylinositol 3-kinase.
• Pathway: 1-Phosphatidyl-myo-inositol Metabolism
• Reaction: a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol) + ATP = a 1,2-diacyl- sn-glycero-3-phospho-(1D-myo-inositol-3-phosphate) + ADP + H⁺
• Enzyme class 3: Chain A: E.C.2.7.1.153 - phosphatidylinositol-4,5-bisphosphate 3-kinase.

Pathway:

• Reaction: a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol-4,5-bisphosphate) + ATP = a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol-3,4,5- trisphosphate) + ADP + H⁺
• Enzyme class 4: Chain A: E.C.2.7.11.1 - non-specific serine/threonine protein kinase.
• 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⁺

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

reference

DOI no: 10.1016/j.bmc.2017.01.012

Bioorg Med Chem Lett 25:1481-1486 (2017)

PubMed id: 28129991

Identification of allosteric binding sites for PI3Kα oncogenic mutant specific inhibitor design.

M.S.Miller, S.Maheshwari, F.M.McRobb, K.W.Kinzler, L.M.Amzel, B.Vogelstein, S.B.Gabelli.

ABSTRACT

No abstract given.