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- Name help_outline 1,2-dioctanoyl-sn-glycero-3-phospho-(1D-myo-inositol-4,5-bisphosphate) Identifier CHEBI:83419 Charge -5 Formula C25H44O19P3 InChIKeyhelp_outline XLNCEHRXXWQMPK-MJUMVPIBSA-I SMILEShelp_outline CCCCCCCC(=O)OC[C@H](COP([O-])(=O)O[C@@H]1[C@H](O)[C@H](O)[C@@H](OP([O-])([O-])=O)[C@H](OP([O-])([O-])=O)[C@H]1O)OC(=O)CCCCCCC 2D coordinates Mol file for the small molecule Search links Involved in 2 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
- Name help_outline ATP Identifier CHEBI:30616 (Beilstein: 3581767) help_outline Charge -4 Formula C10H12N5O13P3 InChIKeyhelp_outline ZKHQWZAMYRWXGA-KQYNXXCUSA-J SMILEShelp_outline Nc1ncnc2n(cnc12)[C@@H]1O[C@H](COP([O-])(=O)OP([O-])(=O)OP([O-])([O-])=O)[C@@H](O)[C@H]1O 2D coordinates Mol file for the small molecule Search links Involved in 1,256 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
- Name help_outline 1,2-dioctanoyl-sn-glycero-3-phospho-(1D-myo-inositol-3,4,5-trisphosphate) Identifier CHEBI:83416 Charge -7 Formula C25H43O22P4 InChIKeyhelp_outline ANFYVAHJWGJYAT-QLCNXWICSA-G SMILEShelp_outline CCCCCCCC(=O)OC[C@H](COP([O-])(=O)O[C@@H]1[C@H](O)[C@H](OP([O-])([O-])=O)[C@@H](OP([O-])([O-])=O)[C@H](OP([O-])([O-])=O)[C@H]1O)OC(=O)CCCCCCC 2D coordinates Mol file for the small molecule Search links Involved in 3 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
- Name help_outline ADP Identifier CHEBI:456216 (Beilstein: 3783669) help_outline Charge -3 Formula C10H12N5O10P2 InChIKeyhelp_outline XTWYTFMLZFPYCI-KQYNXXCUSA-K SMILEShelp_outline Nc1ncnc2n(cnc12)[C@@H]1O[C@H](COP([O-])(=O)OP([O-])([O-])=O)[C@@H](O)[C@H]1O 2D coordinates Mol file for the small molecule Search links Involved in 835 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
- Name help_outline H+ Identifier CHEBI:15378 Charge 1 Formula H InChIKeyhelp_outline GPRLSGONYQIRFK-UHFFFAOYSA-N SMILEShelp_outline [H+] 2D coordinates Mol file for the small molecule Search links Involved in 9,176 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
Cross-references
| RHEA:55632 | RHEA:55633 | RHEA:55634 | RHEA:55635 | |
|---|---|---|---|---|
| Reaction direction help_outline | undefined | left-to-right | right-to-left | bidirectional |
| UniProtKB help_outline |
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Related reactions help_outline
More general form(s) of this reaction
Publications
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Kinetic and structural analyses reveal residues in phosphoinositide 3-kinase alpha that are critical for catalysis and substrate recognition.
Maheshwari S., Miller M.S., O'Meally R., Cole R.N., Amzel L.M., Gabelli S.B.
Phosphoinositide 3-kinases (PI3Ks) are ubiquitous lipid kinases that activate signaling cascades controlling cell survival, proliferation, protein synthesis, and vesicle trafficking. PI3Ks have dual kinase specificity: a lipid kinase activity that phosphorylates the 3'-hydroxyl of phosphoinositide ... >> More
Phosphoinositide 3-kinases (PI3Ks) are ubiquitous lipid kinases that activate signaling cascades controlling cell survival, proliferation, protein synthesis, and vesicle trafficking. PI3Ks have dual kinase specificity: a lipid kinase activity that phosphorylates the 3'-hydroxyl of phosphoinositides and a protein-kinase activity that includes autophosphorylation. Despite the wealth of biochemical and structural information on PI3Kα, little is known about the identity and roles of individual active-site residues in catalysis. To close this gap, we explored the roles of residues of the catalytic domain and the regulatory subunit of human PI3Kα in lipid and protein phosphorylation. Using site-directed mutagenesis, kinetic assays, and quantitative mass spectrometry, we precisely mapped key residues involved in substrate recognition and catalysis by PI3Kα. Our results revealed that Lys-776, located in the P-loop of PI3Kα, is essential for the recognition of lipid and ATP substrates and also plays an important role in PI3Kα autophosphorylation. Replacement of the residues His-936 and His-917 in the activation and catalytic loops, respectively, with alanine dramatically changed PI3Kα kinetics. Although H936A inactivated the lipid kinase activity without affecting autophosphorylation, H917A abolished both the lipid and protein kinase activities of PI3Kα. On the basis of these kinetic and structural analyses, we propose possible mechanistic roles of these critical residues in PI3Kα catalysis. << Less