Process of carboxylation of glutamic acid residues in the gla domain of human des-gamma-carboxyprothrombin.
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.
Uehara
S
S
Department of Gastroenterology, Tonan Hospital, N1, W6, Chuoku, Sapporo, Japan.
Gotoh
K
K
Handa
H
H
Honjo
K
K
Hirayama
A
A
D000328:Adult; D000368:Aged; D020816:Amino Acid Motifs; D000925:Anticoagulants / Q000627:therapeutic use; D015415:Biomarkers; D014408:Biomarkers, Tumor / Q000097:blood* / Q000302:isolation & purification; D019735:Carbon-Carbon Ligases / Q000097:blood*; D006528:Carcinoma, Hepatocellular / Q000097:blood*; D005260:Female; D018698:Glutamic Acid / Q000378:metabolism*; D006801:Humans; D008113:Liver Neoplasms / Q000097:blood*; D008297:Male; D010446:Peptide Fragments / Q000032:analysis; D011498:Protein Precursors / Q000302:isolation & purification*; D011516:Prothrombin / Q000302:isolation & purification*; D014812:Vitamin K / Q000378:metabolism; D014859:Warfarin / Q000627:therapeutic use
D000925:Anticoagulants; D015415:Biomarkers; D014408:Biomarkers, Tumor; D010446:Peptide Fragments; D011498:Protein Precursors; D014812:Vitamin K; D018698:Glutamic Acid; C008208:acarboxyprothrombin; D014859:Warfarin; D011516:Prothrombin; D019735:Carbon-Carbon Ligases; C020660:glutamyl carboxylase