Coagulation factor XII (Hageman factor) Washington D.C.: inactive factor XIIa results from Cys-571----Ser substitution.
Structural studies on a congenital abnormal coagulation factor XII (Hageman factor), factor XII Washington D.C., have been performed to identify the defect responsible for its lack of procoagulant activity. Amino acid sequence analysis of a tryptic peptide isolated from the abnormal factor XII indicated that Cys-571 (equivalent to Cys-220 in the chymotrypsin numbering system) had been replaced by serine. No other substitutions in the active-site triad--namely, His-393, Asp-442, and Ser-544--were found. We propose that the Cys-571----Ser replacement found in this factor XII variant destroys the formation of the disulfide linkage between Cys-540 and Cys-571, giving rise to an altered conformation of the active-site serine residue or the secondary substrate-binding site and, thus, leads to the loss of enzyme activity.
Miyata
T
T
Department of Biology, Faculty of Science, Kyushu University, Fukuoka, Japan.
Kawabata
S
S
Iwanaga
S
S
Takahashi
I
I
Alving
B
B
Saito
H
H
D000595:Amino Acid Sequence; D002851:Chromatography, High Pressure Liquid; D003545:Cysteine; D005174:Factor XII / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D010446:Peptide Fragments / Q000302:isolation & purification; D010449:Peptide Mapping; D011487:Protein Conformation; D012694:Serine; D014357:Trypsin
D010446:Peptide Fragments; C061607:factor XII Washington D.C.; D012694:Serine; D005174:Factor XII; D014357:Trypsin; D003545:Cysteine