title: A common protein fold topology shared by flavonoid biosynthetic enzymes and therapeutic targets.
abstract: The relationship between a natural product's biosynthetic enzyme and its therapeutic target is unknown. The concept of protein fold topologies, as a determining factor in recognition, has been developed through molecular modeling techniques. We have shown that biosynthetic enzymes and the therapeutic targets of three classes of natural products that inhibit protein kinases share a common protein fold topology (PFT) and cavity recognition points despite having different fold type classifications. The clinical agent flavopiridol would have been identified by this new approach.
authors.affiliation: Natural Product Discovery, Eskitis Institute, Griffith University, Brisbane, Queensland, 4111, Australia.
authors.forename: Bernadette M
authors.initials: BM
authors.lastname: McArdle
authors.forename: Marc R
authors.initials: MR
authors.lastname: Campitelli
authors.forename: Ronald J
authors.initials: RJ
authors.lastname: Quinn
mesh_terms: D001688:Biological Products / Q000096:biosynthesis* / Q000737:chemistry / Q000494:pharmacology*; D005419:Flavonoids / Q000737:chemistry*; D008958:Models, Molecular; D015394:Molecular Structure; D010880:Piperidines / Q000737:chemistry*; D010946:Plants, Medicinal / Q000201:enzymology*; D011487:Protein Conformation; D017510:Protein Folding; D047428:Protein Kinase Inhibitors / Q000378:metabolism; D011506:Proteins / Q000737:chemistry*
chemical_list: D001688:Biological Products; D005419:Flavonoids; D010880:Piperidines; D047428:Protein Kinase Inhibitors; D011506:Proteins; C077990:alvocidib