MACCHESS CONSORTIUM FOR PHASING METHODS IN MACROMOLECULAR CRYSTALLOGRAPHY

以下三个项目已从试验中受益 在康奈尔高能同步加速器源上进行。--兰布达 与其他溶菌酶一样，来自Lambda噬菌体的噬菌体溶菌酶 能够分解细菌细胞壁的。然而，这种机制 完成这种水解的方式与 其他溶菌酶(如T4和蛋清溶菌酶)。我们 最近在一种存在的情况下解决了酶的结构 缓蚀剂为2.7埃，通过分子置换。该结构 提供了对这种酶用于 分解细菌细胞壁的肽聚糖层。-真菌 真菌来源的高丝氨酸脱氢酶高丝氨酸脱氢酶 已被证明是抗真菌药物的极好靶点。自.以来 这种370残留酶缺乏任何蛋氨酸，我们一直在追求 用多重同构替换法确定结构参数 三维结构。优化的异常导数数据 在国际象棋F2波束线上收集的数据导致了部分跟踪 这个结构的。不幸的是，严重的不同构间 晶体阻碍了快速发展。-AAC(6‘)-II AAC(6’)-II是 引起细菌抗药性的细菌酶 氨基糖苷类抗生素。硒蛋氨酸的两个MAD数据集 该酶的衍生物是在国际象棋F2束线上收集的。 我们已经成功地解决了结构问题，目前正在精炼 原子模型。这一结构确定的意义 考虑抗生素耐药性的问题是显而易见的。

The following three projects have benefited from experiments performed at the Cornell High Energy Synchrotron Source. -Lambda phage lysozyme lysozyme from lambda phage, like other lysozymes, is capable of hydrolyzing bacterial cell-walls. However, the mechanism by which this hydrolysis is accomplished differs dramatically from that of other lysozymes (e.g. T4 - and hen egg-white lysozyme). We have recently solved the structure of the enzyme in the presence of an inhibitor to 2.7 Angstrom, by molecular replacement. The structure provides insight into the unique mechanism employed by this enzyme for hydrolyzing the peptidoglycan layer of bacterial cell-walls. - fungal homoserine dehydrogenase Homoserine dehydrogenase from fungal sources has been shown to be an excellent target for antifungal agents. Since this 370 residue enzyme lacksany methionines, we have pursued the multiple isomorphous replacement method for determining the three-dimensional structure. Optimized anomalous derivative data collected at the CHESS F2 beam-line has resulted in a partial tracing of the structure. Unfortunately, severe non-isomorphism between crystals has hampered rapid progress. - AAC(6')-Ii AAC(6')-Ii is a bacterial enzyme responsible for bacterial resistance against aminoglycoside antibiotics. Two MAD datasets of a selinomethionine derivative of this enzyme were collected at the CHESS F2 beam-line. We have successfully solved the structure, and are currently refining the atomic model. The significance of this structure determination considering the problem of antibiotic resistance is obvious.