1. Process of carboxylation of glutamic acid residues in the gla domain of human des-gamma-carboxyprothrombin.
- Author
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Uehara S, Gotoh K, Handa H, Honjo K, and Hirayama A
- Subjects
- Adult, Aged, Amino Acid Motifs, Anticoagulants therapeutic use, Biomarkers, Tumor isolation & purification, Female, Humans, Male, Peptide Fragments analysis, Vitamin K metabolism, Warfarin therapeutic use, Biomarkers, Biomarkers, Tumor blood, Carbon-Carbon Ligases blood, Carcinoma, Hepatocellular blood, Glutamic Acid metabolism, Liver Neoplasms blood, Protein Precursors isolation & purification, Prothrombin isolation & purification
- Abstract
In the absence of vitamin K (VK) or in the presence of VK antagonists, hepatic VK-dependent carboxylase activity is inhibited and des-gamma-carboxyprothrombin (DCP) is released into the blood. We analyzed the number of glutamic acid (Glu) residues and their positions in the Gla domain (GD) of DCP to investigate the gamma-carboxylation mechanism of VK-dependent carboxylase. Several DCPs were found in each subject studied. The 10 Gla residues of human prothrombin were carboxylated in order from the N-terminal (residues 26, 25, 16, 29, 20, 19, 14, 32, 7 and 6). The process of Glu carboxylation seemed to proceed three-dimensionally from inside to outside the molecule.
- Published
- 1999
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