Conformational Equilibrium of the Reactive Center Loop of Antithrombin Examined by Steady State and Time-Resolved Fluorescence Measurements:  Consequences for the Mechanism of Factor Xa Inhibition by Antithrombin−Heparin Complexes

• Published in: Biochemistry (Easton) Vol. 40; no. 22; pp. 6680 - 6687
• Main Authors: Futamura, Akiko, Beechem, Joseph M, Gettins, Peter G. W
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 05.06.2001
• Subjects: Allosteric Regulation - genetics; Animals; Antithrombins - chemistry; Antithrombins - genetics; Antithrombins - metabolism; Binding Sites - genetics; Cell Line; Cricetinae; Factor Xa - metabolism; Factor Xa Inhibitors; Fluorescent Dyes - metabolism; Heparin - metabolism; Humans; Macromolecular Substances; Mutagenesis, Site-Directed; Oxadiazoles - metabolism; Protein Conformation; Serine Proteinase Inhibitors - chemistry; Serine Proteinase Inhibitors - genetics; Serine Proteinase Inhibitors - metabolism; Spectrometry, Fluorescence; Thermodynamics

Activation of antithrombin by high-affinity heparin as an inhibitor of factor Xa has been ascribed to an allosteric switch between two conformations of the reactive center loop. However, we have previously shown that other, weaker binding, charged polysaccharides can give intermediate degrees of act...