The formation of a covalent complex between a dipeptide ligand and the src SH2 domain.
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.
Alligood
K J
KJ
Glaxo Wellcome, Inc., Research Triangle Park, North Carolina 27709, USA.
Charifson
P S
PS
Crosby
R
R
Consler
T G
TG
Feldman
P L
PL
Gampe
R T
RT
Gilmer
T M
TM
Jordan
S R
SR
Milstead
M W
MW
Mohr
C
C
Peel
M R
MR
Rocque
W
W
Rodriguez
M
M
Rusnak
D W
DW
Shewchuk
L M
LM
Sternbach
D D
DD
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
D000447:Aldehydes; D004151:Dipeptides; D008024:Ligands; D011506:Proteins; D019000:Phosphotyrosine; D003545:Cysteine