title: Antithrombin Glasgow, 393 Arg to His: a P1 reactive site variant with increased heparin affinity but no thrombin inhibitory activity.
abstract: Antithrombin Glasgow is a hereditary abnormal antithrombin that has lost thrombin inhibitory activity. It was isolated from the plasma of a 41-year-old male with a history of thrombotic events. Antithrombin Glasgow was purified from plasma using heparin-Sepharose chromatography at pH 7.4 eluting with increasing concentrations of NaCl. The normal protein eluted with 0.9 mol/l NaCl and Glasgow with 1.05 mol/l NaCl. Electrophoresis in agarose at pH 8.6 showed the variant to migrate more anodally than normal. The C-terminal small fragment resulting from catalytic cleavage with elastase between P3 and P4 of the reactive loop was isolated and sequenced. This showed the replacement of the arginine at residue 3 by a histidine. This is residue 393 in the intact molecule. The findings suggest that heparin, on binding, interacts indirectly with the reactive centre region of antithrombin.
authors: Department of Clinical Biochemistry, Christchurch Hospital, New Zealand.
authors: M C
authors: MC
authors: Owen
authors: C H
authors: CH
authors: Beresford
authors: R W
authors: RW
authors: Carrell
mesh_terms: D000328:Adult; D000595:Amino Acid Sequence; D000990:Antithrombin III / Q000235:genetics* / Q000302:isolation & purification / Q000378:metabolism; D001120:Arginine; D001665:Binding Sites; D006493:Heparin / Q000378:metabolism; D006639:Histidine; D006801:Humans; D008297:Male; D013917:Thrombin / Q000037:antagonists & inhibitors; D013923:Thromboembolism / Q000097:blood / Q000235:genetics*
chemical_list: C054089:antithrombin III Glasgow; D006639:Histidine; D000990:Antithrombin III; D006493:Heparin; D001120:Arginine; D013917:Thrombin