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.

journal_name

FEBS Lett

journal_title

FEBS letters

authors

Owen MC,Beresford CH,Carrell RW

doi

10.1016/0014-5793(88)80841-x

subject

Has Abstract

pub_date

1988-04-25 00:00:00

pages

317-20

issue

2

eissn

0014-5793

issn

1873-3468

pii

0014-5793(88)80841-X

journal_volume

231

pub_type

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