计算机与应用化学
計算機與應用化學
계산궤여응용화학
COMPUTERS AND APPLIED CHEMISTRY
2009年
12期
1567-1570
,共4页
陈启龙%郑文岭%马文丽%吕顺清
陳啟龍%鄭文嶺%馬文麗%呂順清
진계룡%정문령%마문려%려순청
同源建模%三级结构%SOX4突变%肺癌
同源建模%三級結構%SOX4突變%肺癌
동원건모%삼급결구%SOX4돌변%폐암
homology modeling%tertiary structure%SOX4 mutant%Lung carcinoma
SOX家族与很多人类肿瘤的发牛有关.对人类肺癌组织中的SOX4进行测序,发现该基因HMG-box区有突变发生并导致SOX4蛋白的107密码了发生突变.以三级结构已知的SOX2为模板,采用同源建模方法对突变和正常SOX4蛋白HMG-box进行建模.结果显示突变和正常SOX4蛋白的三级结构很相似,且突变导致107密码子位置的侧链结构不稳定.提示该位置的不稳定可能会影响突变SOX4蛋白侧链的弹性,并有可能影响相应蛋白的功能.表面静电分析显示SOX4蛋白C端有一个可能与其它小分子或蛋白质的相互作用位点的N/C腔.这些结果显示SOX4蛋白的上述空间结构可能与其活性与功能的调控有关,而SOX4突变可能与肺癌的发生和转移有关.
SOX傢族與很多人類腫瘤的髮牛有關.對人類肺癌組織中的SOX4進行測序,髮現該基因HMG-box區有突變髮生併導緻SOX4蛋白的107密碼瞭髮生突變.以三級結構已知的SOX2為模闆,採用同源建模方法對突變和正常SOX4蛋白HMG-box進行建模.結果顯示突變和正常SOX4蛋白的三級結構很相似,且突變導緻107密碼子位置的側鏈結構不穩定.提示該位置的不穩定可能會影響突變SOX4蛋白側鏈的彈性,併有可能影響相應蛋白的功能.錶麵靜電分析顯示SOX4蛋白C耑有一箇可能與其它小分子或蛋白質的相互作用位點的N/C腔.這些結果顯示SOX4蛋白的上述空間結構可能與其活性與功能的調控有關,而SOX4突變可能與肺癌的髮生和轉移有關.
SOX가족여흔다인류종류적발우유관.대인류폐암조직중적SOX4진행측서,발현해기인HMG-box구유돌변발생병도치SOX4단백적107밀마료발생돌변.이삼급결구이지적SOX2위모판,채용동원건모방법대돌변화정상SOX4단백HMG-box진행건모.결과현시돌변화정상SOX4단백적삼급결구흔상사,차돌변도치107밀마자위치적측련결구불은정.제시해위치적불은정가능회영향돌변SOX4단백측련적탄성,병유가능영향상응단백적공능.표면정전분석현시SOX4단백C단유일개가능여기타소분자혹단백질적상호작용위점적N/C강.저사결과현시SOX4단백적상술공간결구가능여기활성여공능적조공유관,이SOX4돌변가능여폐암적발생화전이유관.
sox family has been associated with a variety of human tumors. The SOX4-gene HMG-box of lung cancer tissues was sequenced and identified mutation sites, and cause the codon 107 of SOX4 protein was mutant. The tertiary structures of mutant and normal SOX4 proteins were modeled using homology modeling method, and the known tertiary structure of SOX2 as template. The results showed that the tertiary structures of the mutant and normal SOX4 is similar, and the side-chain conformations of the codon 107 region were relatively unstable. It suggested that the instability of codon 107 might affect the flexibility of the side chains of mutant SOX4 and could affect the functions of the corresponding protein. Analysis of the Electrostatic Surfaces showed the C-terminal half of SOX4 form an N/C cavity where interactions with organic molecules or proteins could be possible. These results indicated that the spatial structure of SOX4 more likely to regulate the activity and function of this protein, and mutations in the SOX4 gene were likely to be associated with lung carcinogenesis and metastasis.