2WXF
The crystal structure of the murine class IA PI 3-kinase p110delta in complex with PIK-39.
Summary for 2WXF
| Entry DOI | 10.2210/pdb2wxf/pdb |
| Related | 2WXE 2WXG 2WXH 2WXI 2WXJ 2WXK 2WXL 2WXM 2WXN 2WXO 2WXP 2WXQ 2WXR |
| Descriptor | PHOSPHATIDYLINOSITOL-4,5-BISPHOSPHATE 3-KINASE CATALYTIC SUBUNIT DELTA ISOFORM, 2-((9H-PURIN-6-YLTHIO)METHYL)-5-CHLORO-3-(2-METHOXYPHENYL)QUINAZOLIN-4(3H)-ONE (3 entities in total) |
| Functional Keywords | transferase, phosphoprotein, isoform-specific inhibitors, cancer |
| Biological source | MUS MUSCULUS (HOUSE MOUSE) |
| Total number of polymer chains | 1 |
| Total formula weight | 108274.57 |
| Authors | Berndt, A.,Miller, S.,Williams, O.,Lee, D.D.,Houseman, B.T.,Pacold, J.I.,Gorrec, F.,Hon, W.-C.,Liu, Y.,Rommel, C.,Gaillard, P.,Ruckle, T.,Schwarz, M.K.,Shokat, K.M.,Shaw, J.P.,Williams, R.L. (deposition date: 2009-11-09, release date: 2010-01-12, Last modification date: 2023-12-20) |
| Primary citation | Berndt, A.,Miller, S.,Williams, O.,Lee, D.D.,Houseman, B.T.,Pacold, J.I.,Gorrec, F.,Hon, W.-C.,Liu, Y.,Rommel, C.,Gaillard, P.,Ruckle, T.,Schwarz, M.K.,Shokat, K.M.,Shaw, J.P.,Williams, R.L. The P110D Structure: Mechanisms for Selectivity and Potency of New Pi(3)K Inhibitors Nat.Chem.Biol., 6:117-, 2010 Cited by PubMed Abstract: Deregulation of the phosphoinositide-3-OH kinase (PI(3)K) pathway has been implicated in numerous pathologies including cancer, diabetes, thrombosis, rheumatoid arthritis and asthma. Recently, small-molecule and ATP-competitive PI(3)K inhibitors with a wide range of selectivities have entered clinical development. In order to understand the mechanisms underlying the isoform selectivity of these inhibitors, we developed a new expression strategy that enabled us to determine to our knowledge the first crystal structure of the catalytic subunit of the class IA PI(3)K p110 delta. Structures of this enzyme in complex with a broad panel of isoform- and pan-selective class I PI(3)K inhibitors reveal that selectivity toward p110 delta can be achieved by exploiting its conformational flexibility and the sequence diversity of active site residues that do not contact ATP. We have used these observations to rationalize and synthesize highly selective inhibitors for p110 delta with greatly improved potencies. PubMed: 20081827DOI: 10.1038/NCHEMBIO.293 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.9 Å) |
Structure validation
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