Conformation of a bound inhibitor of blood coagulant factor Xa

Biochemistry. 2003 Jul 8;42(26):7942-9. doi: 10.1021/bi027369g.

Abstract

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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amidines / chemistry*
  • Binding Sites
  • Factor Xa / chemistry*
  • Factor Xa Inhibitors
  • Humans
  • Imidazoles / chemistry*
  • Magnetic Resonance Spectroscopy / methods
  • Models, Molecular
  • Molecular Conformation
  • Pyridines / chemistry*
  • Trypsin / chemistry

Substances

  • Amidines
  • Factor Xa Inhibitors
  • Imidazoles
  • Pyridines
  • Trypsin
  • Factor Xa