Antithrombin Cambridge II, 384 Ala to Ser. Further evidence of the role of the reactive centre loop in the inhibitory function of the serpins

Perry, D.J., Daly, M., Harper, P.L., Tait, R.C. , Price, J., Walker, I.D. and Carrell, R.W. (1991) Antithrombin Cambridge II, 384 Ala to Ser. Further evidence of the role of the reactive centre loop in the inhibitory function of the serpins. FEBS Letters, 285(2), pp. 248-250. (doi: 10.1016/0014-5793(91)80809-H) (PMID:1906811)

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Abstract

Four unrelated individuals have been identified with an identical antithrombin variant, associated in one of them with episodes of recurrent venous thromboses. In each case, the plasma antithrombin concentration was normal and the only functional abnormality was a minor but consistent decrease in the heparin‐induced thrombin inhibition suggesting a mutation at or near the reactive centre of the molecule. Amplification and direct sequencing of exon 6 showed a G→T mutation at nucleotide 1246, which corresponds to a substitution of a serine for an alanine at residue 384. This is one of a series of conserved alanines that form the stalk to the reactive centre loop. The observed changes in this variant are compatible with recent structural studies that infer that mobility of this stalk with partial re‐entry into the A‐sheet of the molecule is necessary for optimal 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., Daly, M., Harper, P.L., Tait, R.C., Price, J., Walker, I.D., and Carrell, R.W.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing
Journal Name:FEBS Letters
Publisher:Elsevier
ISSN:0014-5793
ISSN (Online):1873-3468

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