STRUCTURE-FUNCTION RELATIONSHIPS OF LYSOSOMAL ENZYMES

溶酶体酶的结构-功能关系

• 批准号: 4690011
• 负责人: R L PROIA
• 金额: --
• 依托单位: NAT INST OF ARTHRITIS, DIABETES, DIGESTIVE & KIDNEY DISEASES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/4690011
• 关键词: DNA; Sandhoff disease; Tay Sachs disease; beta N acetylhexosaminidase; chemical structure function; chromosome aberrations; genetic disorder diagnosis; genetic library; lysosomes; molecular cloning; nucleic acid sequence

e importance of the lysosomal enzyme, Beta-hexosaminidase, is illustrated Tay-Sachs and Sandhoff diseases which are caused by mutations in the zyme's Alpha and Beta chains, respectively. Previously, we had aracterized the normal biosynthetic pathway of the enzyme and the sruption of this pathway in patients with Tay-Sachs disease. In order to vestigate both normal and abnormal aspects of the enzyme at the DNA level, had cloned a cDNA corresponding to the Alpha-chain. Using Alpha-chain NA probes I have screened human genomic libraries constructed in cosmid and cteriophage lambda vectors and have isolated several clones containing the ne for the Alpha-chain. These clones are being extensively characterized restriction mapping, Southern blotting and DNA sequencing. Thus far, the tron-exon organization of 75% of the 20 kilobase Alpha-chain gene has been termined. This work will provide the informational framework for the entual elucidation of mutations in Tay-Sachs disease. In addition, the aracterization of this first lysosomal enzyme gene may provide novel sight into this important class of cellular glycoproteins.

说明了溶酶体酶β-氨基己糖苷酶的重要性 泰-萨二氏病和桑德霍夫病是由基因突变引起的， 酶的α链和β链。 此前，我们有 描述了酶的正常生物合成途径， Tay-Sachs病患者中该通路的破坏。 为了 在DNA水平上研究酶的正常和异常方面， 克隆了一个对应于α链的cDNA。 使用Alpha链 NA探针我筛选了在粘粒中构建的人类基因组文库， λ噬菌体载体，并分离了几个含有 是阿尔法链 这些克隆人被广泛地描述为 限制性酶切图谱、Southern印迹和DNA测序。 到目前为止， 20种淀粉酶α链基因中75%的外显子结构已被发现。 终结 这项工作将提供信息框架， 泰-萨二氏病突变的初步阐明。 此外该 这种第一种溶酶体酶基因的特征化可以提供新的 这类重要的细胞糖蛋白。