Conformation of a bound inhibitor of blood coagulant factor Xa.
13C[(15)N] and (13)C[(19)F] rotational-echo double-resonance NMR have been used to characterize the enzyme-bound structure of ZK-816042, an amidine-imidazoline inhibitor of human factor Xa (FXa). The NMR experiments were performed on a lyophilized FXa-inhibitor complex. The complex was formed in solution in the presence of stabilizing excipients and frozen after gradual supercooling prior to lyophilization. The results indicate that the inhibitor binds with a distribution of orientations of the imidazoline ring.
Studelska
Daniel R
DR
Department of Chemistry, Washington University, St. Louis, Missouri 63130, USA.
McDowell
Lynda M
LM
Adler
Marc
M
O'Connor
Robert D
RD
Mehta
Anil K
AK
Guilford
William J
WJ
Dallas
Jerry L
JL
Arnaiz
Damian
D
Light
David R
DR
Schaefer
Jacob
J
D000578:Amidines / Q000737:chemistry*; D001665:Binding Sites; D015951:Factor Xa / Q000737:chemistry*; D065427:Factor Xa Inhibitors; D006801:Humans; D007093:Imidazoles / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008958:Models, Molecular; D008968:Molecular Conformation; D011725:Pyridines / Q000737:chemistry*; D014357:Trypsin / Q000737:chemistry
D000578:Amidines; D065427:Factor Xa Inhibitors; D007093:Imidazoles; D011725:Pyridines; D014357:Trypsin; D015951:Factor Xa