title: Understanding the impact of the P-loop conformation on kinase selectivity.
abstract: This work addresses the link between selectivity and an unusual, folded conformation for the P-loop observed initially for MAP4K4 and subsequently for other kinases. Statistical and computational analyses of our crystal structure database demonstrate that inhibitors that induce the P-loop folded conformation tend to be more selective, especially if they take advantage of this specific conformation by interacting more favorably with a conserved Tyr or Phe residue from the P-loop.
authors.forename: Cristiano R W
authors.initials: CR
authors.lastname: Guimarães
authors.forename: Brajesh K
authors.initials: BK
authors.lastname: Rai
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Munchhof
authors.forename: Shenping
authors.initials: S
authors.lastname: Liu
authors.forename: Jian
authors.initials: J
authors.lastname: Wang
authors.forename: Samit K
authors.initials: SK
authors.lastname: Bhattacharya
authors.forename: Leonard
authors.initials: L
authors.lastname: Buckbinder
mesh_terms: D030562:Databases, Protein; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism*; D008958:Models, Molecular; D011487:Protein Conformation; D017510:Protein Folding; D047428:Protein Kinase Inhibitors / Q000737:chemistry / Q000494:pharmacology; D013379:Substrate Specificity
chemical_list: D047428:Protein Kinase Inhibitors; D048049:Extracellular Signal-Regulated MAP Kinases; C102548:Mapk4 protein, rat