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研究生:賴政宗
研究生(外文):Cheng-Tsung Lai
論文名稱:胞苷去胺酶超家族之結構分析:相似、相異與預測
論文名稱(外文):Strcutural Analysis of the Cytidine Deaminase Superfamily: Conservation, Divergence and Prediction
指導教授:廖淑惠廖淑惠引用關係
指導教授(外文):Shwu-Huey Liaw
學位類別:碩士
校院名稱:國立陽明大學
系所名稱:遺傳學研究所
學門:生命科學學門
學類:生物訊息學類
論文種類:學術論文
論文出版年:2004
畢業學年度:92
語文別:中文
中文關鍵詞:胞苷去胺酶預測超家族
外文關鍵詞:cytidine deaminasepredictionsuperfamily
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後基因體時代最主要的挑戰之一,就是了解大自然如何使用同一個結構來演化出眾多不同功能的蛋白質。針對同一個結構超家族的同源性蛋白做結構分析,可了解蛋白結構的可塑性與功能多樣性。經由分析,我們發現cytidine deaminase (CDA), fungal cytosine deaminases, 植物及一些細菌guanine deaminase (GD), dCMP deaminase (dCMPD), RNA editing deaminase與riboflavin合成蛋白之一RibG,都同屬於胞苷去胺酶超家族。這些去胺酶催化cytosine, guanine 或者是adenine上的amino group變成keto group。
為了找出每個成員可能參與受質辨認的胺基酸,首先先針對胞苷去胺酶超家族已知的蛋白結構做比較,整理出其相似與相異之處。然後運用序列搜尋、多序列排比、二級結構的預測與已知的資訊做人工微調,找出各家族成員最保留的胺基酸。最後依據預測之結構來判別哪些是參與受質辨認之高度保留的胺基酸。我們結構的分析建議了真核生物之ADARs是源自ADATs, 而ADATs則是源自GD; 而CDARs則源自dCMPD。此外,這些不同去胺酶利用相異的胺基酸與受質的共同ribose及phosphate作用。還發現每一家族有許多高度保留的胺基酸是參與結構穩定,而只有少部分的是參與蛋白功能的多樣性。這些預測結果可幫助對其他成員的了解,尤其是RNA編輯去胺酶; 也可提供未來之突變分析與幫助晶體結構測定。
One major challenge in the post-genomic era is to understand how nature has evolved one structural fold into various proteins for their different functions. Structural analysis of homologous proteins in a structural superfamily would provide an efficient path to understand the structural plasticity for the functional versatility. Our analysis has revealed that cytidine deaminases (CDAs), fungal cytosine deaminases (CDs), plant and some bacterial guanine deaminases (GDs), dCMP deaminases (dCMPD), RNA editing deaminases and riboflavin biosynthesis protein RibG belong to the CDA superfamily. These deaminases catalyze the zinc-assisted conversion of the amino group of the cytosine, guanine or adenine moiety into a keto group.
To identify the putative substrate-recognition residues for each member, a comparative analysis of the available structures in the superfamily was first carried out. Then multiple sequence alignments for each member and for the CDA superfamily were performed by the program ClustalW, followed by manual editing according to the structural information and secondary structure prediction using PSI-PRED. Finally, atomic models were built based on the known structures to reveal whether the conserved residues are potentially localized nearby the active-site cavity. The putative substrate-interacting residues for dCMPD, RibG and RNA-editing deaminase have been identified. Obviously, these deaminases utilize different residues to interact with the common ribose and phosphate groups of their substrates. Our results also reveal that a large portion of the conserved residues are responsible for the superfamily's structural plasticity, whereas only a small portions are directly involved in its functional versatility. These prediction results would provide a structural basis for mutational analysis to elucidate the functional roles of the critical residues.
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