Coagulation factor XII (Hageman factor) Washington D.C. Inactive factor XIIa results from Cys-571 → Ser substitution

T. Miyata, S. I. Kawabata, S. Iwanaga, I. Takahashi, B. Alving, H. Saito

研究成果: ジャーナルへの寄稿記事

35 引用 (Scopus)

抄録

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from the abnormal factor XII indicated that Cys-571 (equivalent to Cys-220 in the chymotrypsin numbering system) had been replaced by serine.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.

元の言語英語
ページ(範囲)8319-8322
ページ数4
ジャーナルProceedings of the National Academy of Sciences of the United States of America
86
発行部数21
DOI
出版物ステータス出版済み - 1 1 1989

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Factor XIIa
Factor XII
Serine
Catalytic Domain
Protein Sequence Analysis
Chymotrypsin
Disulfides
Binding Sites
Peptides
Enzymes

All Science Journal Classification (ASJC) codes

  • General

これを引用

Coagulation factor XII (Hageman factor) Washington D.C. Inactive factor XIIa results from Cys-571 → Ser substitution. / Miyata, T.; Kawabata, S. I.; Iwanaga, S.; Takahashi, I.; Alving, B.; Saito, H.

:: Proceedings of the National Academy of Sciences of the United States of America, 巻 86, 番号 21, 01.01.1989, p. 8319-8322.

研究成果: ジャーナルへの寄稿記事

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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from the abnormal factor XII indicated that Cys-571 (equivalent to Cys-220 in the chymotrypsin numbering system) had been replaced by serine.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.",
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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.

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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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