Conformation of antithrombin III with defective biological functions derived from a thrombophilic patient

Antithrombin III (AT III) with defective biological functions and altered antigenicity has been found in a thrombophilic patient. Circular dichroism (CD) spectra of antithrombin III purified from the patient's plasma were measured in near and far-ultraviolet (UV) wavelength regions. The far-UV CD spectrum of the patient's AT III was similar at room temperature to that of normal AT III derived from healthy adult males. Mean residue ellipticity at 221 nm of the patient's AT III, however, decreased its magnitude by 6% gradually as temperature increased up to 74 degrees C, whereas that of the normal AT III reduced its magnitude sharply at around 63-64 degrees C and by 18%. The near-UV CD spectrum of patient's AT III was different from that of normal AT III. These results indicate that the secondary structure of patient's AT III is similar to that of normal AT III at room temperature, while local conformation of aromatic amino acid residues in the abnormal protein is different from that in the normal one and that the secondary structure of the patient's AT III is heat-stable, while that of the normal one is heat-labile.