title: 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.forename: D L
authors.initials: DL
authors.lastname: Diuguid
authors.forename: M J
authors.initials: MJ
authors.lastname: Rabiet
authors.forename: B C
authors.initials: BC
authors.lastname: Furie
authors.forename: H A
authors.initials: HA
authors.lastname: Liebman
authors.forename: B
authors.initials: B
authors.lastname: Furie
mesh_terms: D000595:Amino Acid Sequence; D004247:DNA / Q000032:analysis; D005164:Factor IX / Q000235:genetics* / Q000378:metabolism; D006467:Hemophilia A / Q000097:blood / Q000235:genetics*; D006801:Humans; D007700:Kinetics; D009154:Mutation; D010743:Phospholipids / Q000097:blood; D011485:Protein Binding; D011487:Protein Conformation; D011498:Protein Precursors / Q000235:genetics* / Q000378:metabolism
chemical_list: D010743:Phospholipids; D011498:Protein Precursors; C049838:factor IX Cambridge; D005164:Factor IX; D004247:DNA