Artigo Acesso aberto Revisado por pares

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

ISSN

1873-3468

Autores

Stephen O. Brennan, J.Y. Borg, Peter M. George, Claudine Soria, Jeannette Soria, Jacques Caen, Robin W. Carrell,

Tópico(s)

Protease and Inhibitor Mechanisms

Resumo

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.

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