Elucidation of the steric bases of anticancer activities of interferons through a combined approach by X-ray crystal structure analyzes and protein engineering.

1) x射线衍射仪系统的搭建。本拨款购买的“衍射x射线束记录装置”，已完成使用成像板的二维x射线衍射仪的设置。2)电脑绘图系统的设置。本补助金所购买的“中央处理器升级系统”已成功纳入现有系统，大幅提升其效能。3)小鼠干扰素β晶体结构的细化使用上述系统1)和2)，该结构已在2.15 A分辨率下细化到r因子为19.1%。广泛的修改是必要的A-Helix部分(EMBO杂志4,3193-3201 (1993)；也提交给j.m l. biol。)4)预测各种I型干扰素的三维结构。对以下四种干扰素进行了结构预测：human-alpha，human-beta，牛和羊的tau's。针对I型干扰素的结构-活性关系研究的大量数据集被编译并基于已建立的三维结构进行系统评估（Pharmacology & Therapeutics, 58,93-132(1993)）。5)人类α干扰素结晶的又一挑战。[参考译文]这次尝试和以前一样失败了，这表明不结晶性一定有一些根本的原因。使用动态光散射装置（例如）的更系统的方法是必要的。

1) Set-up of the X-ray diffractometer system.The "recording device for diffracted X-ray beam", whcih was purchased by the present grant, completed the set-up of the two-dimensional X-ray diffraactometer using Imaging Plates.2) Set-up of the computer graphics system.The "CPU-upgrading system" purchased by the present grant, was succesfully incorporated into the existing system extensively upgrading its performance.3) Refinement of the crystal structure of murine interferon-betaUsing the systems 1) and 2) above, the structure has been refined at 2.15 A resolution to an R-factor of 19.1%. Extensive modification was found necessary for the A-Helix portion (EMBO Journal 4,3193-3201 (1993) ; also submitted to J.Mol.Biol.)4) Prediction of the three-dimensional structures for various Type I interferons.Structure prediction was done for the following four interferons : human-alphaD,human-beta, bovine & ovine tau's. A huge data set of the structure-activity relationship studiesdirected for Type I interferons were compiled and systematically evaluated based on the established three-dimensional structure(Pharmacology & Therapeutics, 58,93-132 (1993)).5) Yet another challenege for the crystallization of human interferon-alpha.13EA10 : The attempt failed as before indicating that there must be some fundamental reason for non-crystallizability. More systematic approaches making use of a dynamic light scattering device (for example) would be necessary.