title: NMR structure of a potent small molecule inhibitor bound to human keratinocyte fatty acid-binding protein.
abstract: The NMR structure is presented for compound 1 (BMS-480404) (Ki = 33 (+/-2) nM) bound to keratinocyte fatty acid-binding protein. This article describes interactions between a high affinity drug-like compound and a member of the fatty acid-binding protein family. A benzyl group ortho to the mandelic acid in 1 occupies an area of the protein that fatty acids do not normally contact. Similar to that in the kFABP-palmitic acid structure, the acid moiety in 1 is proximal to R129 and Y131. Computational modeling indicates that the acid moiety in 1 interacts indirectly via a modeled water molecule to R109.
authors.affiliation: Bristol-Myers Squibb Pharmaceutical Research Institute, P.O. Box 4000, Princeton, New Jersey 08543, USA. patricia.mcdonnell@bms.com
authors.forename: Patricia A
authors.initials: PA
authors.lastname: McDonnell
authors.forename: Keith L
authors.initials: KL
authors.lastname: Constantine
authors.forename: Valentina
authors.initials: V
authors.lastname: Goldfarb
authors.forename: Stephen R
authors.initials: SR
authors.lastname: Johnson
authors.forename: Richard
authors.initials: R
authors.lastname: Sulsky
authors.forename: David R
authors.initials: DR
authors.lastname: Magnin
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Robl
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Caulfield
authors.forename: Rex A
authors.initials: RA
authors.lastname: Parker
authors.forename: David S
authors.initials: DS
authors.lastname: Taylor
authors.forename: Leonard P
authors.initials: LP
authors.lastname: Adam
authors.forename: William J
authors.initials: WJ
authors.lastname: Metzler
authors.forename: Luciano
authors.initials: L
authors.lastname: Mueller
authors.forename: Bennett T
authors.initials: BT
authors.lastname: Farmer
mesh_terms: D001665:Binding Sites; D003198:Computer Simulation; D050556:Fatty Acid-Binding Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D015603:Keratinocytes / Q000378:metabolism*; D008024:Ligands; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D015394:Molecular Structure
chemical_list: D050556:Fatty Acid-Binding Proteins; D008024:Ligands