New carbohydrate site in mutant antithrombin (7 Ile→Asn) with decreased heparin affinity
Authors:
- Peter M. GeorgePGPeter M. George
- 12 September 1988
- journal article
- case report
- Published by Wiley in FEBS Letters
- Vol. 237 (1-2) , 118-122
Abstract
A mutant antithrombin was isolated from the plasma of a patient with pulmonary embolism. The new protein, which accounted for 55% of the antithrombin, had decreased heparin affinity and contained two components when analysed on the basis of either charge or molecular mass. Sialidase and endo‐β‐N‐acetylglucosaminidase F treatment suggested that this heterogeneity was due to a partial glycosylation occurring at a new carbohydrate attachment sequence. Peptide mapping by reverse‐phase HPLC showed that the abnormality involved the N‐terminal tryptic peptide. Sequence analysis demonstrated that the underlying mutation was 7 Ile→Asn which introduces a new Asn‐Cys‐Thr glycosylation sequence. This new oligosaccharide attachment site occupies the base of the proposed heparin‐binding site, and the finding explains the consequent decrease in heparin affinity.Keywords
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