NMR-based, molecular dynamics- and random walk molecular mechanics-supported study of conformational aspects of a carbohydrate ligand (Gal beta 1-2Gal beta 1-R) for an animal galectin in the free and in the bound state.
The binding of a carbohydrate to a lectin may affect the conformation of the ligand. To address this question for the galectin from chicken liver, the conformation of Gal beta 1-2Gal beta 1-R was analyzed in the free and in the galectin-bound state with 2D-ROESY- and 1D- as well as 2D-transferred NOE-experiments. A computer-assisted analysis of spatial parameters of the ligand by molecular dynamics (MD) and random walk molecular mechanics (RAMM) calculations, taking different dielectric constraints from epsilon = 1 to epsilon = 80 and various force fields into account, were instrumental to define the energetic minima of the free state. NMR-derived interresidual distance constraints enabled a conformational mapping. The two overlapping interresidual distance constraints obtained from transferred-NOE experiments of the galectin-ligand complex clearly support the notion that the conformation of the disaccharide in the bound state is at least very close to its global energy minimum state in solution.
Siebert
H C
HC
Institut für Physiologische Chemie, Tierärztliche Fakultät, Ludwig-Maximilians-Universität, München, Germany.
Gilleron
M
M
Kaltner
H
H
von der Lieth
C W
CW
Kozár
T
T
Bovin
N
N
Korchagina
E Y
EY
Vliegenthart
J F
JF
Gabius
H J
HJ
D000818:Animals; D002236:Carbohydrate Conformation; D002240:Carbohydrate Sequence; D002645:Chickens; D003196:Computer Graphics; D037161:Galectins; D006388:Hemagglutinins / Q000302:isolation & purification / Q000378:metabolism*; D008024:Ligands; D008099:Liver / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009844:Oligosaccharides / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism*
D037161:Galectins; D006388:Hemagglutinins; D008024:Ligands; D009844:Oligosaccharides