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Next Article 
Heparin binding defect in a new antithrombin III variant: Rouen, 47 Arg to
His
MC Owen, JY Borg, C Soria, J Soria, J Caen and RW Carrell
Antithrombin III (AT-III) Rouen is a hereditary abnormal antithrombin with
normal progressive inhibitory activity and reduced heparin cofactor
activity. It was isolated from the plasma of a woman who suffered a sudden
idiopathic sensorineural hearing loss and balance impairment. There was no
familial history of thrombosis. By heparin- Sepharose chromatography,
AT-III Rouen was separated from the normal antithrombin on elution with
increasing concentrations of NaCl. AT-III Rouen eluted earlier than is
normal at both pH 7.4 and pH 6.0. At the lower pH, the antithrombins bound
more avidly to the column, with the abnormal AT-III eluting closer to the
normal than at the higher pH. Two- dimensional peptide mapping of tryptic
and Staphylococcus aureus V8 protease digests of carboxymethylated
antithrombins was performed on thin-layer silica plates. The abnormal
peptide was located by tryptophan staining, and amino acid analysis and
sequence studies demonstrated a substitution of an arginine at residue 47
for a histidine. Results from this study suggest that replacement of
arginine 47 by a partially positively charged histidine has less effect on
the heparin binding affinity than dose replacing it with a neutral cysteine
side chain as in AT-III Toyama, in which no heparin binding was observed.
In addition, heparin binding per se is not a sufficient condition to
activate AT-III.
Volume 69,
Issue 5,
pp. 1275-1279,
05/01/1987
Copyright © 1987 by The American Society of Hematology
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