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New carbohydrate site in mutant antithrombin (7 Ile→Asn) with decreased heparin affinity
Author(s) -
Brennan Stephen O.,
Borg Jeanne-Yvonne,
George Peter M.,
Soria Claudine,
Soria Jeannette,
Caen Jacques,
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)80183-2
Subject(s) - antithrombin , chemistry , glycosylation , heparin , biochemistry , oligosaccharide , mutant , peptide , gene
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.