Conformation of a Bound Inhibitor of Blood Coagulant Factor Xa
- 17 June 2003
- journal article
- Published by American Chemical Society (ACS) in Biochemistry
- Vol. 42 (26) , 7942-7949
- https://doi.org/10.1021/bi027369g
Abstract
13C{15N} and 13C{19F} 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.Keywords
This publication has 19 references indexed in Scilit:
- Investigation of the Binding of Epimer A of the Covalent Hydrate of 6,7-Bis(trifluoromethyl)-8-d-ribityllumazine to a Recombinant F22W Bacillus subtilis Lumazine Synthase Mutant by 15N{19F} REDOR NMRThe Journal of Organic Chemistry, 2002
- Factorising ligand affinity: a combined thermodynamic and crystallographic study of trypsin and thrombin inhibition†Journal of Molecular Biology, 2001
- Preparation, Characterization, and the Crystal Structure of the Inhibitor ZK-807834 (CI-1031) Complexed with Factor Xa,Biochemistry, 2000
- Crystal Structures of Human Factor Xa Complexed with Potent InhibitorsJournal of Medicinal Chemistry, 2000
- Conformations of Trypsin-Bound Amidine Inhibitors of Blood Coagulant Factor Xa by Double REDOR NMR and MD SimulationsJournal of Medicinal Chemistry, 1999
- Investigation of the Binding of Fluorolumazines to the 1-MDa Capsid of Lumazine Synthase by 15N{19F} REDOR NMRJournal of the American Chemical Society, 1999
- Structural and Functional Analyses of Benzamidine-Based Inhibitors in Complex with Trypsin: Implications for the Inhibition of Factor Xa, tPA, and UrokinaseJournal of Medicinal Chemistry, 1998
- Discovery of N-[2-[5-[Amino(imino)methyl]-2-hydroxyphenoxy]-3,5-difluoro- 6-[3-(4,5-dihydro-1-methyl-1H-imidazol-2-yl)phenoxy]pyridin-4-yl]-N-methylglycine (ZK-807834): A Potent, Selective, and Orally Active Inhibitor of the Blood Coagulation Enzyme Factor XaJournal of Medicinal Chemistry, 1998
- Crystal structures of factor Xa specific inhibitors in complex with trypsin: structural grounds for inhibition of factor Xa and selectivity against thrombinFEBS Letters, 1995
- Structure of Human Des(1-45) Factor Xa at 2·2 Å ResolutionJournal of Molecular Biology, 1993