ゼラチナーゼ活�?�ドメインのホモロジーモデリングと阻害剤とのドッキングスタディ

Chem-Bio Informatics Journal

柴田 智之²  松原 亜紀¹  玉木 和彦³  大岩 玲子²  岩田 依子²  丹沢 和比古¹  宮本 �?�?² 

[1] 三共株式会社 第二生物研究�?;三共株式会社 創薬化学研究�?;三共株式会社 化学研究�?

关键词: Homology Modeling;    Docking Study;    MMP;    Gelatinase;    Collagenase;    Inhibitor;    ホモロジーモデリング;    ドッキングスタディ;    MMP;    ゼラチナーゼ;    コラーゲナーゼ;    阻害剤;   

DOI  :  10.1273/cbij.1.23

学科分类：生物化学/生物物理

来源: Chem-Bio Informatics Society

【 摘 要 】

References(30)Three-dimensional models of the gelatinase catalytic domains were built from collagenase structures by the homology modeling technique. The docking of different types of inhibitors was then studied in an attempt to obtain structural insight into their binding modes. In the case of an amide compound docked with gelatinase A, almost the same binding mode was obtained as that observed in the crystal structure of another amide compound complexed with collagenase. With respect to our series of matlystatin analogs, the key hydrogen bonding and hydrophobic interactions with gelatinase B were similar to those of the above amide compounds, although these derivatives have a unique piperazine ring. The length and hydrophobic nature of the S1' subsite was well consistent with the observation that the inhibitory activity rises as the alkyl chain at P1' becomes longer. The binding mode of a sulfonamide inhibitor was slightly different from that of amide and piperazine inhibitors, but similar to that proposed recently for another sulfonamide inhibitor.

【 授权许可】

Unknown