Two novel antithrombin variants, Asn187Asp and Asn187Lys, indicate a functional role for asparagine 187

Perry, D.J., Marshall, C., Borg, J.-Y., Tait, R.C. , Daly, M.E., Walker, I.D. and Carrell, R.W. (1995) Two novel antithrombin variants, Asn187Asp and Asn187Lys, indicate a functional role for asparagine 187. Blood Coagulation and Fibrinolysis, 6(1), pp. 51-54. (doi: 10.1097/00001721-199502000-00008) (PMID:7795154)

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Abstract

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.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Tait, Dr Robert and Walker, Prof Isobel
Authors: Perry, D.J., Marshall, C., Borg, J.-Y., Tait, R.C., Daly, M.E., Walker, I.D., and Carrell, R.W.
College/School:College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing
Journal Name:Blood Coagulation and Fibrinolysis
Publisher:Lippincott, Williams & Wilkins
ISSN:0957-5235
ISSN (Online):1473-5733

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