Elucidation of the cause for reduced activity of abnormal human plasmin containing an Ala55‐Thr mutation: importance of highly conserved Ala55 in serine proteases

FEBS Letters

Umeyama, Hideaki¹  Takeda-Shitaka, Mayuko¹ 

[1]School of Pharmaceutical Sciences, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo 108-8641, Japan

关键词: Serine protease;    Plasmin;    Homology modeling;    Molecular dynamics simulation;    BOTR;    bovine trypsin;    HUPL;    serine protease domain of human plasmin;    MD simulation;    molecular dynamics simulation;    loop 5–6;    loop between 5 and 6 β-strands in the N-terminal domain of serine protease;   

DOI  :  10.1016/S0014-5793(98)00280-4

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

In serine proteases, Ala⁵⁵ is highly conserved and located just behind the catalytic triad. That the activity of human plasmin is reduced by the A55T substitution indicates the importance of Ala⁵⁵ in catalysis. In the present study, the 3-D model of A55T human plasmin shows that an unusual hydrogen bond between Thr⁵⁵ Oγ1 and His⁵⁷ Nϵ2 alters His⁵⁷ into an inactive conformation in which His⁵⁷ cannot accept a proton from Ser¹⁹⁵ as a catalytic base. Our results demonstrate that Ala⁵⁵ contributes heavily to the active conformation of His⁵⁷ and ensures the proton transfer from Ser¹⁹⁵ to His⁵⁷.

【 授权许可】

Unknown