Back to Search
Start Over
Structural basis for the high-affinity binding of pyrrolotriazine inhibitors of p38 MAP kinase.
- Source :
-
Acta crystallographica. Section D, Biological crystallography [Acta Crystallogr D Biol Crystallogr] 2008 Jul; Vol. D64 (Pt 7), pp. 705-10. Date of Electronic Publication: 2008 Jun 18. - Publication Year :
- 2008
-
Abstract
- The crystal structure of unphosphorylated p38alpha MAP kinase complexed with a representative pyrrolotriazine-based inhibitor led to the elucidation of the high-affinity binding mode of this class of compounds at the ATP-binding site. The ligand binds in an extended conformation, with one end interacting with the adenine-pocket hinge region, including a hydrogen bond from the carboxyl O atom of Met109. The other end of the ligand interacts with the hydrophobic pocket of the binding site and with the backbone N atom of Asp168 in the DFG activation loop. Addition of an extended benzylmorpholine group forces the DFG loop to flip out of position and allows the ligand to make additional interactions with the protein.
- Subjects :
- Binding Sites
Crystallography, X-Ray
Humans
Mitogen-Activated Protein Kinase 14 antagonists & inhibitors
Models, Molecular
Protein Binding
Anilides chemistry
Benzamides chemistry
Mitogen-Activated Protein Kinase 14 chemistry
Protein Kinase Inhibitors chemistry
Pyrimidines chemistry
Pyrroles chemistry
Subjects
Details
- Language :
- English
- ISSN :
- 0907-4449
- Volume :
- D64
- Issue :
- Pt 7
- Database :
- MEDLINE
- Journal :
- Acta crystallographica. Section D, Biological crystallography
- Publication Type :
- Academic Journal
- Accession number :
- 18566506
- Full Text :
- https://doi.org/10.1107/S0907444908010032