跳到主要內容

臺灣博碩士論文加值系統

(18.204.56.185) 您好!臺灣時間:2022/08/14 03:16
字體大小: 字級放大   字級縮小   預設字形  
回查詢結果 :::

詳目顯示

我願授權國圖
: 
twitterline
研究生:陳昆河
研究生(外文):Chen, Kuen-Ho
論文名稱:由分子動力模擬的方式研究存在於第三型心臟蛇毒的束縛水現象
論文名稱(外文):Molecular Dynamics Simulations Studying for the Bound Water Found in Cardiotoxin III (A3)
指導教授:黃鎮剛呂平江
指導教授(外文):Jenn-Kang HwangPing-Chiang Lyu
學位類別:碩士
校院名稱:國立清華大學
系所名稱:生命科學系
學門:生命科學學門
學類:生物學類
論文種類:學術論文
論文出版年:2002
畢業學年度:90
語文別:英文
論文頁數:44
中文關鍵詞:分子動力模擬束縛水心臟蛇毒
外文關鍵詞:Molecular Dynamics SimulationBound WaterCardiotoxin III
相關次數:
  • 被引用被引用:0
  • 點閱點閱:148
  • 評分評分:
  • 下載下載:0
  • 收藏至我的研究室書目清單書目收藏:0
蛇是會讓人害怕的動物之一,蛇毒更是讓人與其他動物死亡的主要原因,因為毒液會引起溶血作用,破壞紅血球,有些也會造成血液的凝結等。在本論文裡首先概略的提到目前的實驗報告,目前將眼鏡蛇毒蛋白分成三大類:心臟毒 (Cardiotoxin)、神經毒 (Neurotoxin)、和磷脂水解酵素 (Phospholipase A2)。
台灣眼鏡蛇心臟毒素被分析後,發現有五種蛋白,命為CTX A1~A5,接著從序列中Pro30和Ser28存在與否,將這五種分成P型和S型兩類。其中比較有意思的是,發現在台灣眼鏡蛇毒蛋白中,第三型心臟蛇毒有束縛水 (bound water) 的現象,第三型心臟蛇毒是屬於P型的,由三維結構來看,束縛水存在於第二個迴圈 (loop II) 內,而束縛水的功用,目前是認為它與迴圈上的某幾個胺基酸產生氫鍵,氫鍵網可以穩定其上方β-摺板 (β-sheet) 的結構。
本論文中,我們從熱力學中Gibbs自由能的觀點,藉由分子動力模擬的計算方式,用經驗價鍵模型 (Empirical valence bond model),以及自由能微擾法 (Free energy perturbation method) 的方法,代替實驗上真實蛋白質的突變,有效的計算出自由能差的變化量,來研究此現象並用以解釋第二迴圈上的Proline30胺基酸的重要。

Snake venoms make people die often and snakes only live by them. They consist of cardiotoxin (CTX), neurotoxin, and phospholipase A2 (PLA2). From the published reports, there are five kinds of venom proteins in the CTX molecules found in Taiwan cobra (Naja naja atra) venom, and they were named CTX A1~A5. Next, CTX proteins have been classified into two types, P-type and S-type, which are distinguished by the presence of Pro30 and Ser28, respectively, near the tip of loop II.
An interesting phenomenon called "bound water" was found in recent reports. By the NMR experiments, this water molecule exists in loop II of CTX A3 protein, which is a P-type protein. It is possible for its function to form a hydrogen-binding network in loop II, and this network may keep the above β-sheet structures stable.
In this thesis, we study this phenomenon by molecular dynamics simulations. We first mutate Pro30 to Gly by using the empirical valence bond model. And then by using the free energy perturbation method, we calculate the free energy differences. From the point of view of the thermodynamic cycle, we can get the values of ΔΔG, the changes of the Gibbs free energy differences. The meaning of ΔΔG is to discuss the effects of mutation of side chains with bound water on protein. Finally, after comparing the results of P-type proteins with S-type ones, we suggest that the amino acid, Pro30, may be a "key" for the bound water. Namely, although Pro30 is not directly bound with the bound water by hydrogen bonds, this residue still affects this bound water molecule.

CONTENTS
I. Introduction 1
I-1.Snake venom, 2
I-2.Overall structure of CTX, 3
I-3.Function of CTX, 4
I-4.The aim of this thesis, 6
II. Principle and methods 15
II-1.Thermodynamic cycle, 16
II-2.Empirical Valence Bond model, 17
II-3.Free Energy Perturbation method, 19
III. Results 21
IV. Conclusion 24
References 26

References
Arms, K. & Mcpheeters, D. (1975) "Sensitivity of cultured embryonic heart cells to cardiotoxin obtained from Naja naja siamensis venom" Toxicon 13, 333-338
Alan Fersht, Structure and Mechanism in Protein Science (W. H. Freeman and Company, New York, 1999)
Arieh Warshel, Computer modeling of chemical reactions in enzymes and solutions (John Wiley & Sons, New York, 1991)
Chen, Y-H., Hu, C-T., & Yang, J-T. (1984) "Membrane disintergratic and hemolysis of human erythrocytes by snake venom cardiotoxin (a membrane-disruptive polypeptide)" Biochem. Int. 8, 329-338
Chien, K-Y., Chiang, C-M., Hseu, Y-C., Vyas, A. A., Rule, G. S., & Wu, W. (1994) "Two Distinct Types of Cardiotoxin as Revealed by the Structure and Activity Relationship of Their Interaction with Zwitterionic Phospholipid Dispersions" J. Biol. Chem. 269, 14473-14483
Fletcher, J. E., Jiang, M-H. (1993) Toxicon 31, 669-695
Fletcher, J. E., Jiang, M-S., Gong, Q-H., Yudkowsky, M. L., & Wieland, S. J. (1991) "Effects of a cardiotoxin from Naja naja kaouthia venom on skeletal muscle: involvement of calcium-induced calcium release, sodium ion currents and phospholipases A2 and C" Toxicon 29, 1489-1500
Hanahan, D. J. (1986) Annu. Rev. Biochem. 55, 483-520
Harvey, A. L. & Hayashi, K. (1987) "Depolarization of Skeletal Muscle Cells in Culture by a Cardiotoxin-like Basic Polypeptide from the Venom of The Taiwan Cobra (Naja naja atra)" Toxicon 25, 681-684
Hodges, S. J., Agbij, A. S., Harvey, A. L., &Hinder, R. C. (1987) "Cobra cardiotoxin: purification effects on skeletal muscle and structural activity relationships" Eur. J. Biochem. 165, 373-383
Hseu, Y. &Wu, W. (1995) "Interaction between Cardiotoxin and Phospholipase A2 in Membranes as Revealed by the Synergistic Effect of Their in Vitro Activity" FASEB J., A1371
Jiang, M. S., Fletcher, J. E., & Smith, L. A. (1989) "Factors Influencing the Hemmolysis of Human Erythrocytes by Cardiotoxin from Naja naja kaouthia and Naja naja atra Venoms and a Phospholipase A2 with Cardiotoxin-like Activities from Bungarus fasciatus Venom" Toxicon 27, 247-257
Kini, R. M., Haar, N. C., & Evans, H. J. (1989) "Non-enzymatic Inhibitors of Coagulation and Platelet Aggregation from Naja nigricollis Venom are Cardiotoxin" Biochem. Biophys. Res.Commun. 150, 1012-1016
Lee, C. Y., Chang, C. C., Chiu, P. J. S., Tseng, T. C., & Lee, S. Y. (1968) "Pharmacological Properties of Cardiotoxin Isolated from formasan Cobra Venom" Naunyn-Schmiedebergs Arch. Pharmacol. 12, 265-286
Lee, C. Y. (1972) "Chemistry and Pharmacology of Polypeptide Toxins in Snake Venom" Ann. Rev. Pharmacol. 12, 265-286
Levitt, M., (1978) Biochemistry 17, 4277-4285
Patel, H. V., Vyas, A. A., Vyas, K. A., Liu, Y-S., Chiang, C-M., Chi, L-M., & Wu, W. (1997) J. Biol. Chem. 272, 1484-1492
Sarker, N. K. (1947) "Isolation of cardiotoxin from Cobra venom (Naja tripudians, monocelate variety)" J. Indian. Chem. Soc. 24, 227-232
Sue, S-C., Harold, J., Brisson, J. R., Wu, W. (2001) "Dynamic Characterization of the Water Binding Loop in the P-Type Cardiotoxin: Implication for the Role of the Bound Water Molecule" Biochemistry 40, 12782-12794
Sun, J. J. & Walker, M. J. A. (1986) "Actions of Cardiotoxin from the Southern Chinese Cobra (Naja naja atra) on Rat Cardiac Tissue" Toxicon 24, 233-245
Sun, Y-J., Wu, W., Chiang, C-M., Hsin, A-Y., & Hsiao, C-D. (1997) "Crystal structure of cardiotoxin V from Taiwan cobra venom: pH-dependent conformational change and a novel membrane binding motif identified in the three-finger loops of P-type cardiotoxin" Biochemistry 36, 2403-2413
Takechi, M., Tanaka, Y., & Hayashi, K. (1986) "Binding of Cardiotoxin Analogue III from Formosan Cobra Venom to FL Cells" FEBS Lett. 205, 143-146
Tsetlin, V. (1999) "Snake venom alpha-neurotoxins and other 'three-finger' protein" Eur. J. Biochem. 264(2), 281-286
Vyas, A. A., Pan, J-J., Patel, H. V., Vyas, K. A., Chiang, C-M., Sheu, Y-C., Hwang, J-K., & Wu, W. (1997) J. Biol. Chem. 272, 9661-9670
Vyas, K. A., Patel, H. V., Vyas, A. A., & Wu, W. (1998) Biochemistry 37, 4527-4534
Wolff, J., Salabe, H., Ambrose, M. & Larson, P. R. (1968) "The basic proteins of cobra venom" J. Biol. Chem. 243, 1290-1296

QRCODE
 
 
 
 
 
                                                                                                                                                                                                                                                                                                                                                                                                               
第一頁 上一頁 下一頁 最後一頁 top