1997年5月
Binding mode of CA074, a specific irreversible inhibitor, to bovine cathepsin B as determined by X-ray crystal analysis of the complex
JOURNAL OF BIOCHEMISTRY
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- 巻
- 121
- 号
- 5
- 開始ページ
- 974
- 終了ページ
- 977
- 記述言語
- 英語
- 掲載種別
- 研究論文(学術雑誌)
- 出版者・発行元
- JAPANESE BIOCHEMICAL SOC
The binding mode of CA074 [N-(L-3-trans-propylcarbamoyl-oxirane-2-carbonyl)-L-isoleucyl-L-proline] , a specific irreversible inhibitor, to bovine spleen cathepsin B was elucidated by X-ray crystal structure analysis of the complex at 2.2 Angstrom resolution (conventional R=0.185), Inconsistently with our model used for the development of CA074, the L-isoleucyl-L-proline and propylcarbamoyl moieties are located at the S' and S subsites respectively, This unexpected binding is primarily due to (i) similar extended chain conformations (due to the same S configurations) at the oxirane C2 and C3 atoms of CA074 and (ii) the just fit formation of double hydrogen bonds between the carboxyl oxygens of L-proline and the imidazole nitrogens of His-110 and His-ill residues (these residues are missing in papain, the tertiary structure of which was used for the design of CA074), The oxirane C3 atom possessing the P' substituent is covalently bound to the Cys-29 S gamma atom (C3-S gamma=1.79 Angstrom) and the S configuration is maintained. The present result will provide useful information for characterizing the substrate-specificity of cathepsin B.
- リンク情報
- ID情報
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- ISSN : 0021-924X
- CiNii Articles ID : 10005458320
- Web of Science ID : WOS:A1997WY02200026