INHIBITED COMPLEXES OF HUMAN TYPE I 17: DRUG DESIGN TARGET IN BREAST CANCER

利用稀有过渡金属的酶对 帮助我们了解独特的酶反应。甲酸脱氢酶H (FDH)就是这样一种酶。外佣含有多种氧化还原成分 中心，其中包括钼掺杂辅因子、铁硫化物 在其活性部位有一个天然的硒半胱氨酸残基。这 蛋白质与其他脱氢酶没有序列同源性 它们都有众所周知的蛋白质结合折叠。我们希望了解 这类酶利用钼蝶呤和钼的机制 来调节他们的氧化还原反应。另一个独特的类 其催化机制尚不清楚的酶是 血液转换酶、α-N-乙酰氨基半乳糖苷酶(a-NAGAL)和 α-半乳糖苷酶(α-GAL)。人血中ABO抗原的特异性 是由末端单糖的性质和连接决定的 糖蛋白或糖脂的碳水化合物链 嵌入细胞膜。一种方法来提供大型 O型血的量是将A、B群细胞转化为 O通过使用适当的外切糖苷酶。了解 碳水化合物链转化机理的研究 三维结构的确定有望提供 产生同时含有A和B的酶所需的信息 转换函数。

Enzymes that utilize rare transition metals are of interest to help us understand unique enzymic reactions. Formate dehydrogenase H (FDH) from E. coli is such an enzyme. FDH contains multiple redox centers, which include a molybdopterin cofactor, an iron-sulfur cluster and a natural selenocystein residue at its active site. This protein shares no sequence homology with other dehydrogenases which all have the well-known protein binding fold. We hope to understand the mechanism of this class of enzymes that utilizes molybdopterin and selenocystein to mediate their redox reaction. Another unique class of enzymes whose catalytic mechanism is not understood is that of the blood converting enzymes, a-N-acetylgalactosaminidase (a-NAGAL) and a-galactosidase (a-GAL). The ABO antigenic specificity in human blood is determined by the nature and linkage of monosaccharides at the end of the carbohydrate chains of either glycoproteins or glycolipids embedded in the cell membrane. An approach to providing large quantities of group O blood is to convert group A and B cells to group O by using the appropriate exoglycosidases. Understanding the mechanism of conversion of the carbohydrate chains through three-dimensional structure determination will hopefully provide the information necessary to produce an enzyme with both A and B converting function.