title: Coagulation factor XII (Hageman factor) Washington D.C.: inactive factor XIIa results from Cys-571----Ser substitution.
abstract: 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from the abnormal factor XII indicated that Cys-571 (equivalent to Cys-220 in the chymotrypsin numbering system) had been replaced by serine.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.
authors.affiliation: Department of Biology, Faculty of Science, Kyushu University, Fukuoka, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Miyata
authors.forename: S
authors.initials: S
authors.lastname: Kawabata
authors.forename: S
authors.initials: S
authors.lastname: Iwanaga
authors.forename: I
authors.initials: I
authors.lastname: Takahashi
authors.forename: B
authors.initials: B
authors.lastname: Alving
authors.forename: H
authors.initials: H
authors.lastname: Saito
mesh_terms: 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
chemical_list: D010446:Peptide Fragments; C061607:factor XII Washington D.C.; D012694:Serine; D005174:Factor XII; D014357:Trypsin; D003545:Cysteine