2 NOVEL ANTITHROMBIN VARIANTS, ASN187ASP AND ASN187LYS, INDICATE A FUNCTIONAL-ROLE FOR ASPARAGINE 187

被引:7
作者
PERRY, DJ
MARSHALL, C
BORG, JY
TAIT, RC
DALY, ME
WALKER, ID
CARRELL, RW
机构
[1] UNIV CAMBRIDGE,CTR MRC,DEPT HAEMATOL,CAMBRIDGE CB2 2QH,ENGLAND
[2] CHRU ROUEN,DEPT HEMATOL,F-76031 ROUEN,FRANCE
[3] GLASGOW ROYAL INFIRM,DEPT HAEMATOL,THROMBOSIS RES GRP,GLASGOW G4 0SF,LANARK,SCOTLAND
基金
英国惠康基金;
关键词
ANTITHROMBIN; MUTATION; VENOUS THROMBOSIS;
D O I
10.1097/00001721-199502000-00008
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Three unrelated families have been identified with mutations involving asparagine 187. Two of these families are asymptomatic and were identified during the screening of random blood donors, whilst the third has a history of recurrent thromboembolic disease. In two families the mutation (6460 AAC-->GAC) results in an asparagine to aspartate substitution and is associated with normal immunological levels of antithrombin but a reduction in functional activity. In the third family the mutation (6462 AAC-->AAA) results in an asparagine to lysine substitution at residue 187 and is associated with a parallel reduction in both immunological and functional antithrombin levels. Asparagine 187 is located in the middle of the F helix of antithrombin and forms the major link between the F helix and strand 3 of the A sheet. The F helix is seen to overlie the A sheet of the molecule and moves with strands 2 and 3 of this sheet as they open to allow entry of the reactive site loop to form strand 4. Substitutions of asparagine 187 are, therefore, likely to disrupt this sliding movement leading to a loss of inhibitory activity.
引用
收藏
页码:51 / 54
页数:4
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