Antithrombin Chicago, amino acid substitution of arginine 393 to histidine.
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Erdjument H, Lane DA, Panico M, Di Marzo V, Morris HR, Bauer K, Rosenberg RD
Antithrombin Chicago, amino acid substitution of arginine 393 to histidine.
Thromb Res. 1989 Jun 15;54(6):613-9.
- PubMed ID
- 2781509 [ View in PubMed]
- Abstract
Antithrombin Chicago is a functionally inactive antithrombin variant whose inheritance is associated with thrombotic disease. The variant antithrombin was isolated from plasma of the propositus by chromatography on heparin-Sepharose, followed by passage through thrombin-Sepharose to remove the normal antithrombin component that is present. A pool of fragments ("CNBr pool 4") containing the reactive site region was prepared from the reduced and S-carboxymethylated variant by cleavage with cyanogen bromide followed by reverse-phase HPLC. Sequential treatment of CNBr pool 4 with trypsin and V8 protease produced peptides whose molecular masses were then determined by fast atom bombardment mass spectrometry. The variant protein digests were characterised by a reduction of a peptide of mass 1086, corresponding to the normal antithrombin sequence Ala382-Arg393. However, they contained a peptide of mass 1748, which arises when Arg393 is replaced by His in the sequence Ala382-Arg399. It is concluded that the functional and clinical abnormalities of antithrombin Chicago are all probably caused by a single amino acid substitution, Arg393 to His.