title: The formation of a covalent complex between a dipeptide ligand and the src SH2 domain.
abstract: The X-ray crystal structure of the src SH2 domain revealed the presence of a thiol residue (Cys 188) located proximal to the phosphotyrosine portion of a dipeptide ligand. An aldehyde bearing ligand (1) was designed to position an electrophilic carbonyl group in the vicinity of the thiol. X-ray crystallographic and NMR examination of the complex formed between (1) and the src SH2 domain revealed a hemithioacetal formed by addition of the thiol to the aldehyde group with an additional stabilizing hydrogen bond between the acetal hydroxyl and a backbone carbonyl.
authors.affiliation: Glaxo Wellcome, Inc., Research Triangle Park, North Carolina 27709, USA.
authors.forename: K J
authors.initials: KJ
authors.lastname: Alligood
authors.forename: P S
authors.initials: PS
authors.lastname: Charifson
authors.forename: R
authors.initials: R
authors.lastname: Crosby
authors.forename: T G
authors.initials: TG
authors.lastname: Consler
authors.forename: P L
authors.initials: PL
authors.lastname: Feldman
authors.forename: R T
authors.initials: RT
authors.lastname: Gampe
authors.forename: T M
authors.initials: TM
authors.lastname: Gilmer
authors.forename: S R
authors.initials: SR
authors.lastname: Jordan
authors.forename: M W
authors.initials: MW
authors.lastname: Milstead
authors.forename: C
authors.initials: C
authors.lastname: Mohr
authors.forename: M R
authors.initials: MR
authors.lastname: Peel
authors.forename: W
authors.initials: W
authors.lastname: Rocque
authors.forename: M
authors.initials: M
authors.lastname: Rodriguez
authors.forename: D W
authors.initials: DW
authors.lastname: Rusnak
authors.forename: L M
authors.initials: LM
authors.lastname: Shewchuk
authors.forename: D D
authors.initials: DD
authors.lastname: Sternbach
mesh_terms: D000447:Aldehydes; D000595:Amino Acid Sequence; D001665:Binding Sites; D018360:Crystallography, X-Ray; D003545:Cysteine; D004151:Dipeptides / Q000138:chemical synthesis / Q000737:chemistry*; D006860:Hydrogen Bonding; D008024:Ligands; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D019000:Phosphotyrosine; D011487:Protein Conformation; D011506:Proteins / Q000737:chemistry*; D018909:src Homology Domains
chemical_list: D000447:Aldehydes; D004151:Dipeptides; D008024:Ligands; D011506:Proteins; D019000:Phosphotyrosine; D003545:Cysteine