New carbohydrate site in mutant antithrombin (7 Ile→Asn) with decreased heparin affinity
1988; Wiley; Volume: 237; Issue: 1-2 Linguagem: Inglês
10.1016/0014-5793(88)80183-2
ISSN1873-3468
AutoresStephen O. Brennan, J.Y. Borg, Peter M. George, Claudine Soria, Jeannette Soria, Jacques Caen, Robin W. Carrell,
Tópico(s)Protease and Inhibitor Mechanisms
ResumoA 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.
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