TY - JOUR
T1 - Coagulation factor XII (Hageman factor) Washington D.C.
T2 - Inactive factor XIIa results from Cys-571 → Ser substitution
AU - Miyata, T.
AU - Kawabata, S. I.
AU - Iwanaga, S.
AU - Takahashi, I.
AU - Alving, B.
AU - Saito, H.
PY - 1989
Y1 - 1989
N2 - 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from the abnormal factor XII indicated that Cys-571 (equivalent to Cys-220 in the chymotrypsin numbering system) had been replaced by serine.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.
AB - 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from the abnormal factor XII indicated that Cys-571 (equivalent to Cys-220 in the chymotrypsin numbering system) had been replaced by serine.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.
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U2 - 10.1073/pnas.86.21.8319
DO - 10.1073/pnas.86.21.8319
M3 - Article
C2 - 2510163
AN - SCOPUS:0024853669
SN - 0027-8424
VL - 86
SP - 8319
EP - 8322
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 21
ER -