Molecular basis of hemophilia B: a defective enzyme due to an unprocessed propeptide is caused by a point mutation in the factor IX precursor.

Abstract:

:A mutant factor IX, designated factor IXCambridge, was isolated from a patient with hemophilia B. This protein includes an 18-residue propeptide attached to the NH2 terminus of factor IX. A point mutation at residue -1, from an arginine to a serine, precludes cleavage of the propeptide by a processing protease and interferes with gamma-carboxylation of the factor IX, indicating the importance of the leader sequence in substrate recognition by the vitamin K-dependent carboxylase. This represents an example of an enzyme defect due to the presence of a point mutation in a precursor protein (preproenzyme) that is the cause of a human hereditary disease. This defect will serve as a prototype for understanding the molecular basis of some forms of hemophilia and other hereditary enzyme deficiencies.

authors

Diuguid DL,Rabiet MJ,Furie BC,Liebman HA,Furie B

doi

10.1073/pnas.83.16.5803

subject

Has Abstract

pub_date

1986-08-01 00:00:00

pages

5803-7

issue

16

eissn

0027-8424

issn

1091-6490

journal_volume

83

pub_type

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