Antithrombin Budapest 3. An antithrombin variant with reduced heparin affinity resulting from the substitution L99F.

Abstract:

:The molecular basis and functional properties of a variant antithrombin (AT) protein. AT Budapest 3, were studied. A single base substitution was identified in codon 99, CTC----TTC, altering the normal leucine to phenylalanine. The proband presented with a history of venous thrombotic disease and was found to be homozygous for the mutation. The variant protein demonstrated reduced heparin affinity and reduced antiproteinase activity in the presence of either unfractionated heparin or the AT-binding heparin pentasaccharide, when compared to normal AT. A small change in the isoelectric point was also identified. The substituted amino acid residue of AT Budapest 3 is located near to the proposed AT heparin binding site, and it is suggested that reduced heparin affinity of the variant protein may result from substitution-induced distortion of positive charge geometry in the binding site and/or changes in its position relative to the rest of the inhibitor molecule.

journal_name

FEBS Lett

journal_title

FEBS letters

authors

Olds RJ,Lane DA,Boisclair M,Sas G,Bock SC,Thein SL

doi

10.1016/0014-5793(92)80854-a

keywords:

subject

Has Abstract

pub_date

1992-04-06 00:00:00

pages

241-6

issue

3

eissn

0014-5793

issn

1873-3468

pii

0014-5793(92)80854-A

journal_volume

300

pub_type

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