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Antithrombin Glasgow, 393 arg to his: A P 1 reactive site variant with increased heparin affinity but no thrombin inhibitory activity
Author(s) -
Owen Maurice C.,
Beresford Charles H.,
Carrell Robin W.
Publication year - 1988
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/0014-5793(88)80841-x
Subject(s) - antithrombin , chemistry , thrombin , heparin , affinity chromatography , microbiology and biotechnology , biochemistry , elastase , residue (chemistry) , agarose , enzyme , medicine , biology , platelet
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 P 3 and P 4 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.