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研究生:薛光隆
研究生(外文):Kuang-Lung Hsueh
論文名稱:以核磁共振光譜探討臺灣眼鏡蛇心臟毒素V與肝素衍生雙醣的交互作用
論文名稱(外文):NMR studies on the interactions of heparin derived disaccharide with cobra cardiotoxin V (CTX A5)
指導教授:吳文桂
指導教授(外文):Wen-guey Wu
學位類別:碩士
校院名稱:國立清華大學
系所名稱:生物資訊與結構生物研究所
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
論文頁數:114
中文關鍵詞:心臟毒素肝素選擇激發擴散係數硫化
外文關鍵詞:cardiotoxinheparinselective excitationDOSYsulfation
相關次數:
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  • 下載下載:17
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在此論文中將討論臺灣眼鏡蛇毒素V與醣胺素衍生雙醣的交互作用。心臟毒素有毒殺細胞的作用,且能造成大範圍的發炎反應與組織壞死。而醣胺素是心臟蛇毒的可能目標以標定欲攻擊的特定細胞。
心臟毒素V為相當特異的同源心臟毒素之一,在指環I與指環II的變異使得它表現對於脂質以及醣胺素有較高的親合力,毒性變低,且至今未發現它真正的目標。我們的結果顯示,心臟毒素V與醣胺素的結合可能是經由指環II來結合,由蛋白NOE連結的訊號改變,推測其局部的構形改變,並由auto-docking與x-ray結晶的多餘電子密度,也初步證實了由指環II結合的結果。與先前的心臟蛇毒III與雙醣結合的結構比較,心臟毒素V擁有一個全新的結合位置。且心臟毒素V也會對於醣胺素上不同的硫化區域,表現不同的親合力。這些數據顯示了不同的心臟毒素對醣胺素有不同的結合位置,而肝素上的硫化區域,也對結合有決定性的影響,此結果也表示了心臟毒素V對醣的辨示能力。
In this thesis,we are going to investigate the interaction of the heparinderived disaccharide with the cardiotoxin V (CTX A5). Cardiotoxinswill envenom the target cells and might cause severe necrosis and inflammation ,and glycosaminoglycan serve as potential target within
the process. The distinct loop regions of CTX A5 differs by two inserts and mutations on the loop I and II make it exhibit much higher affinity to glycosaminoglycans and lipids than other cardiotoxin homologues.
From our result of auto-docking and the preliminary x-ray structure suggest the binding of heparin derived disaccharide to CTX A5 is through loop II region and induces protein local conformation change. Compared
with the former complex structure CTX A3, CTX A5 complex shows a novel binding site which is consist with the long-chain heparin SPR data. And the binding specificities is proven to depend on the sulfation motif of the disaccharide, thus suggest recognition of CTX A5 to
glycosaminoglycans.
1.緒論.....1
1.1心臟毒素簡介
1.2心臟毒素的作用模式
1.3醣胺素簡介
1.4研究目的
2.核磁共振探討蛋白與醣胺素的交互作用方法簡介.....13
2.1化學位移
2.2選擇激發實驗
2.3核磁共振在蛋白與醣胺素的研究
3.材料與方法.....17
3.1純化
3.2核磁共振樣品準備與儀器
3.3光譜處理與化學位移的分析
3.4一維選擇激發實驗
3.5模擬-自動嵌入
3.6擴散係數譜
4.結果.....25
4.1心臟毒素A5的性質
4.2結晶的條件
4.3心臟毒素A5與肝素結合的實驗
4.4不同硫化的雙醣
4.5選擇激發的實驗
4.6擴散係數譜
4.7遠紅外光光譜
4.8自動嵌入與結合位置
5.討論.....31
5.1pH值的對心臟毒素的作用
5.2pH對全硫化雙醣與蛋白結合模式的影響
5.3全硫化肝素雙醣的滴定
5.4不同的肝素雙醣對心臟毒素A5的親合力的改變
5.5局部構形的改變
5.6選擇激發的實驗
5.7自動嵌入與晶體的結構比較
6.結論.....41
7.附錄.....97
7.1中英對照表
7.2英文縮寫表
7.3胺基酸縮寫表
7.4溶液的作用
7.5心臟毒素A5的初步結構
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