过氧化氢导致线粒体DNA编码细胞色素C氧化酶基因突变与其编码蛋白结构与功能关系的研究  

Study on correlation of mitochondrial genome mutation and construction and function of it's encoding protein by hydrogen peroxide

作　　者：蔡黔[1] 周红[2] 徐淑芬[1] 肖光夏[2] 刘毅[1] 

机构地区：[1]兰州军区兰州总医院,甘肃兰州730050 [2]第三军医大学西南医院烧伤研究所,重庆630038

出　　处：《中国现代医学杂志》2004年第1期60-63,68,共5页China Journal of Modern Medicine

基　　金：国家"973"重点基础研究发展规划专项经费资助项目 (G19990 5 42 0 2 )

摘　　要：目的　探讨过氧化氢 (H2 O2 )导致线粒体DNA(mtDNA)编码细胞色素C氧化酶 (COX)基因损伤(突变 )后对其编码蛋白结构与功能的影响及两者之间的关系。方法　采用生物信息学技术 ,运用计算机同源模建的方法模拟人天然COX亚单位和其突变体的空间结构 ,并利用已有的实验数据 ,结合模建的结果进行了结构、功能的分析、研究。结果　在COXⅠ的三维结构中突变的部位 (残基 2 97～ 30 6 )位于分子的最外部 ,而该区域参与了与B亚基 (相当于COXⅡ亚基 )的作用 ,该部位的突变使突变部位附近残基的侧链结构环境发生了极大的变化 ,导致附近的电荷性质、亲疏水性质和空间特性出现变化 ,这些变化对酶复合物的形成有直接的影响 ;COXⅡ突变后 ,组成分子结构的“椅靠”部分和“椅面”部分之间的夹角略有增大 ,而“椅靠”和“椅面”之间的夹角的变化将会影响整个酶分子的稳定性。结论　H2 O2 导致的mtDNA编码COXⅠ、COXⅡ亚基基因突变使其编码的COX蛋白空间结构发生改变 ,这种改变是其功能改变 (如酶蛋白活性下降 )的主要原因。Objective:To investigate the change of the structure and function of cytochrome coxidase(COX) due to the mitochondrial encoding COX gene mutation by hydrogen peroxide, and its correlation.Methods:Bioinformatics and computer homology modeling methods were used to predict the space structure of the proteins coded by mutant genes. Combined the experiment data with modeling results,relationship between were analyzed structure-function .Results:The result showed that mutagenesis site located in the outer part of the molecular in COX Ⅰ's three dimensional structure. This site participated in the interaction with B subunit (equal to COX Ⅱ ). Compare the structure of wild type and mutant type COX Ⅰ ,The mutation leaded to a great change of residues around the side chain structure. Electric charges, nature of hydrophilic or hydrophobio and characteristics changed greatly, which directly influenced the formation of enzyme complex.Meanwhile,the angle between back-chair and chain cushion which composes molecule structure become slightly larger after COX Ⅱ mutagenesis occurred. COX Ⅱ subunit located in the inner of the enzyme of the crystal structure of COX. As the back-chair also took part in the interaction with other subunits, so the change of angle would influence the stability of enzyme molecule.Conclusions:Mitochondrial encoding COX gene mutation induced by H 2O 2 can change the space structure of COX,this change is the major cause of enzyme function' decrease.

关 键 词：过氧化氢 DNA 线粒体 编码基因 细胞色素C氧化酶 

分 类 号：R394.3[医药卫生—医学遗传学]