分子动力学研究F<sub>1</sub>-ATP合酶对三磷酸腺苷的稳定和定位作用

引用本文: 伍绍贵, 高晓彤, 李权, 廖杰, 徐成刚. 分子动力学研究F₁-ATP合酶对三磷酸腺苷的稳定和定位作用[J]. 物理化学学报, 2015, 31(9): 1803-1809. doi: 10.3866/PKU.WHXB201508062 shu

Citation: WU Shao-Gui, GAO Xiao-Tong, LI Quan, LIAO Jie, XU Cheng-Gang. F₁-ATPase Stabilizes and Positions Adenosine Triphosphate Revealed by Molecular Dynamics Simulations[J]. Acta Physico-Chimica Sinica, 2015, 31(9): 1803-1809. doi: 10.3866/PKU.WHXB201508062 shu

分子动力学研究F₁-ATP合酶对三磷酸腺苷的稳定和定位作用

伍绍贵 ^1,2, ,
高晓彤 ^1, ,
李权 ^1, ,
廖杰 ^1, ,
徐成刚 ^1,

基金项目:
国家自然科学基金(11405113) (11405113)

四川省科技厅项目(2010JY0122) (2010JY0122)

四川师范大学科学研究基金(10MSL02)资助 (10MSL02)

摘要:

F₁-ATP合酶通过与ATP之间建立广泛的相互作用, 实现对ATP的位置进行精确的定位. 这些相互作用为ATP的合成/水解创造了稳定的环境. 理解这些相互作用是理解ATP的合成/水解机理的基础. 我们通过分子动力学模拟方法研究这些相互作用, 找出在稳定化过程中起到重要作用的残基. 通过检测ATP和F₁-ATP合酶之间的非键相互作用, 发现残基段158-164所形成的loop区域及残基R189, Y345对ATP存在显著相互作用. 其中, 该loop区域对ATP的三磷酸部分形成一个半包围结构, 封闭活性位点区域, 并通过氢键网络约束ATP三磷酸的运动, 为ATP合成/水解创造稳定的环境. 此外, 关键残基Y345通过π-π叠加相互作用对ATP的碱基进行约束, 但是ATP的碱基可以在平行于Y345芳香环的平面内进行滑动, 我们推断这种滑动运动有利于促进ATP的水解.

关键词:

F₁-ATP合酶
/ 氢键
/ 分子动力学
/ 突变

English

F₁-ATPase Stabilizes and Positions Adenosine Triphosphate Revealed by Molecular Dynamics Simulations

1.
1 College of Chemistry and Material Science, Sichuan Normal University, Chengdu 610068, P. R. China;
2 State Key Laboratory of Theoretical Physics, Institute of Theoretical Physics, Chinese Academy of Sciences, Beijing 100190, P. R. China
Received Date: 17 April 2015
Available Online: 06 September 2015
Fund Project:
国家自然科学基金(11405113)

四川省科技厅项目(2010JY0122)

四川师范大学科学研究基金(10MSL02)资助

Abstract:

F₁-ATPase makes extensive interactions with ATP through forming a network of interactions around ATP. These interactions create a steady environment for ATP synthesis/hydrolysis. Thus understanding these interactions between ATP and F₁-ATPase is essential for understanding ATP synthesis/hydrolysis mechanism. We performed all-atom molecular dynamics (MD) simulations to elucidate these interactions and attempted to identify key residues which play important roles in stabilizing and positioning ATP. By examining the non-bonded energies between ATP and residues of βTP subunit in F₁-ATPase, it is found that residues 158-164, R189, Y345 have significant interactions with ATP. The loop segment (residues 158-164) and R189 surround ATP by a half and they interact with β and γ phosphates through forming a network of hydrogen bonds to constraint the motion of ATP triphosphate. The interaction network seals off the conformation of the catalytic site, creating a steady environment for ATP synthesis/hydrolysis. Additionally, ATP base is positioned by the π-π stacking interaction from Y345. However, ATP base can slide and move paralleling to the aromatic group of Y345. It is deduced that this motion may facilitate ATP hydrolysis.

Key words:

1. [1]
  
  (1) Ueno, H.; Suzuki, T.; Kinosita, K.; Yoshida, M. Proc. Natl. Acad. Sci. U. S. A. 2005, 102, 1333. doi: 10.1073/pnas.0407857102
  (1) Ueno, H.; Suzuki, T.; Kinosita, K.; Yoshida, M. Proc. Natl. Acad. Sci. U. S. A. 2005, 102, 1333. doi: 10.1073/pnas.0407857102
2. [2]
  (2) (a) Mitchell, P. Nature 1961, 191, 144. doi: 10.1038/191144a0(2) (a) Mitchell, P. Nature 1961, 191, 144. doi: 10.1038/191144a0
3. [3]
  (b) Rastogi, V. K.; Girvin, M. E. Nature 1999, 402, 263.(b) Rastogi, V. K.; Girvin, M. E. Nature 1999, 402, 263.
4. [4]
  (3) (a) Abrahams, J. P.; Leslie, A.; Lutter, R.; Walker, J. E. Nature 1994, 370, 621. doi: 10.1038/370621a0(3) (a) Abrahams, J. P.; Leslie, A.; Lutter, R.; Walker, J. E. Nature 1994, 370, 621. doi: 10.1038/370621a0
5. [5]
  (b) Zhou, Y.; Duncan, T. M.; Cross, R. L. Proc. Natl. Acad. Sci. U. S. A. 1997, 94, 10583.(b) Zhou, Y.; Duncan, T. M.; Cross, R. L. Proc. Natl. Acad. Sci. U. S. A. 1997, 94, 10583.
6. [6]
  (c) Okuno, D.; Iino, R.; Noji, H. J. Biochem. 2011, 149, 655.(c) Okuno, D.; Iino, R.; Noji, H. J. Biochem. 2011, 149, 655.
7. [7]
  (d) Iino, R.; Hasegawa, R.; Tabata, K. V.; Noji, H. J. Biol. Chem. 2009, 284, 17457.(d) Iino, R.; Hasegawa, R.; Tabata, K. V.; Noji, H. J. Biol. Chem. 2009, 284, 17457.
8. [8]
  (4) Al-Shawi, M. K.; Nakamoto, R. K. Biochemistry 1997, 36, 12954. doi: 10.1021/bi971477z(4) Al-Shawi, M. K.; Nakamoto, R. K. Biochemistry 1997, 36, 12954. doi: 10.1021/bi971477z
9. [9]
  (5) Masaike, T.; Mitome, N.; Noji, H.; Muneyuki, E.; Yasuda, R.; Kinosita, K.; Yoshida, M. J. Exp. Biol. 2000, 203, 1.(5) Masaike, T.; Mitome, N.; Noji, H.; Muneyuki, E.; Yasuda, R.; Kinosita, K.; Yoshida, M. J. Exp. Biol. 2000, 203, 1.
10. [10]
  (6) Dittrich, M.; Schulten, K. J. Bioenerg. Biomembr. 2005, 37, 441. doi: 10.1007/s10863-005-9487-7(6) Dittrich, M.; Schulten, K. J. Bioenerg. Biomembr. 2005, 37, 441. doi: 10.1007/s10863-005-9487-7
11. [11]
  (7) Da, L. T.; Avila, F. P.; Wang, D.; Huang, X. PLOS Comput. Biol. 2013, 9, e1003020.(7) Da, L. T.; Avila, F. P.; Wang, D.; Huang, X. PLOS Comput. Biol. 2013, 9, e1003020.
12. [12]
  (8) (a) Moustafa, I. M.; Shen, H.; Morton, B.; Colina, C. M.; Cameron, C. E. J. Mol. Biol. 2011, 410, 159. doi: 10.1016/j.jmb.2011.04.078(8) (a) Moustafa, I. M.; Shen, H.; Morton, B.; Colina, C. M.; Cameron, C. E. J. Mol. Biol. 2011, 410, 159. doi: 10.1016/j.jmb.2011.04.078
13. [13]
  (b) Hammes-Schiffer, S.; Benkovic, S. J. Annu. Rev. Biochem. 2006, 75.(b) Hammes-Schiffer, S.; Benkovic, S. J. Annu. Rev. Biochem. 2006, 75.
14. [14]
  (9) Zhang, H.; Lu, J. R.; Mu, J. B.; Liu, J. B.; Yang, X. Y.; Wang, M. J.; Zhang, R. B. Acta Phys. -Chim. Sin. 2015, 31, 566. [张贺, 卢俊瑞, 穆江蓓, 刘金彪, 杨旭云, 王美君, 张瑞波. 物理化学学报, 2015, 31, 566.] doi: 10.3866/PKU.WHXB201501061(9) Zhang, H.; Lu, J. R.; Mu, J. B.; Liu, J. B.; Yang, X. Y.; Wang, M. J.; Zhang, R. B. Acta Phys. -Chim. Sin. 2015, 31, 566. [张贺, 卢俊瑞, 穆江蓓, 刘金彪, 杨旭云, 王美君, 张瑞波. 物理化学学报, 2015, 31, 566.] doi: 10.3866/PKU.WHXB201501061
15. [15]
  (10) Ai, Y. X.; Lu, J. R.; Xin, C. W.; Mu, J. B.; Yang, X. Y.; Zhang, H. Acta Phys. -Chim. Sin. 2015, 30, 559. [艾义新, 卢俊瑞, 辛春伟, 穆江蓓, 杨旭芸, 张贺. 物理化学学报, 2014, 30, 559.]. doi: 10.3866/PKU.WHXB201401132(10) Ai, Y. X.; Lu, J. R.; Xin, C. W.; Mu, J. B.; Yang, X. Y.; Zhang, H. Acta Phys. -Chim. Sin. 2015, 30, 559. [艾义新, 卢俊瑞, 辛春伟, 穆江蓓, 杨旭芸, 张贺. 物理化学学报, 2014, 30, 559.]. doi: 10.3866/PKU.WHXB201401132
16. [16]
  (11) Wu, S. G.; Sun, T.; Zhou, P.; Zhou, J. Acta Phys. -Chim. Sin. 2012, 28, 978. [伍绍贵, 孙婷, 周萍, 周俊. 物理化学学报, 2012, 28, 978.] doi: 10.3866/PKU.WHXB201202142(11) Wu, S. G.; Sun, T.; Zhou, P.; Zhou, J. Acta Phys. -Chim. Sin. 2012, 28, 978. [伍绍贵, 孙婷, 周萍, 周俊. 物理化学学报, 2012, 28, 978.] doi: 10.3866/PKU.WHXB201202142
17. [17]
  (12) Duan, Y.; Wu, C.; Chowdhury, S.; Lee, M. C.; Xiong, G.; Zhang, W.; Yang, R.; Cieplak, P.; Luo, R.; Lee, T. J. Comput. Chem. 2003, 24, 1999.(12) Duan, Y.; Wu, C.; Chowdhury, S.; Lee, M. C.; Xiong, G.; Zhang, W.; Yang, R.; Cieplak, P.; Luo, R.; Lee, T. J. Comput. Chem. 2003, 24, 1999.
18. [18]
  (13) Meagher, K. L.; Redman, L. T.; Carlson, H. A. J. Comput. Chem. 2003, 24, 1016. doi: 10.1002/jcc.v24:9(13) Meagher, K. L.; Redman, L. T.; Carlson, H. A. J. Comput. Chem. 2003, 24, 1016. doi: 10.1002/jcc.v24:9
19. [19]
  (14) Bowler, M. W.; Mont mery, M. G.; Leslie, A. G.; Walker, J. E. J. Biol. Chem. 2007, 282, 14238. doi: 10.1074/jbc.M700203200(14) Bowler, M. W.; Mont mery, M. G.; Leslie, A. G.; Walker, J. E. J. Biol. Chem. 2007, 282, 14238. doi: 10.1074/jbc.M700203200
20. [20]
  (15) Miyamoto, S.; Kollman, P. A. J. Comp. Chem. 1992, 13, 952.(15) Miyamoto, S.; Kollman, P. A. J. Comp. Chem. 1992, 13, 952.
21. [21]
  (16) (a) Essmann, U.; Perera, L.; Berkowitz, M. L.; Darden, T.; Lee, H.; Pedersen, L. G. J. Chem. Phys. 1995, 103, 8577. doi: 10.1063/1.470117(16) (a) Essmann, U.; Perera, L.; Berkowitz, M. L.; Darden, T.; Lee, H.; Pedersen, L. G. J. Chem. Phys. 1995, 103, 8577. doi: 10.1063/1.470117
22. [22]
  (b) Darden, T.; York, D.; Pedersen, L. J. Chem. Phys. 1993, 98, 10089.(b) Darden, T.; York, D.; Pedersen, L. J. Chem. Phys. 1993, 98, 10089.
23. [23]
  (17) Berendsen, H. J.; Postma, J. P. M.; van Gunsteren, W. F.; DiNola, A.; Haak, J. J. Chem. Phys. 1984, 81, 3684. doi: 10.1063/1.448118(17) Berendsen, H. J.; Postma, J. P. M.; van Gunsteren, W. F.; DiNola, A.; Haak, J. J. Chem. Phys. 1984, 81, 3684. doi: 10.1063/1.448118
24. [24]
  (18) Bussi, G.; Donadio, D.; Parrinello, M. J. Chem. Phys. 2007, 126, 014101. doi: 10.1063/1.2408420(18) Bussi, G.; Donadio, D.; Parrinello, M. J. Chem. Phys. 2007, 126, 014101. doi: 10.1063/1.2408420
25. [25]
  (19) Hess, B.; Bekker, H.; Berendsen, H. J.; Fraaije, J. G. J. Comput. Chem. 1997, 18, 1463.(19) Hess, B.; Bekker, H.; Berendsen, H. J.; Fraaije, J. G. J. Comput. Chem. 1997, 18, 1463.
26. [26]
  (20) Oster, G.; Wang, H. Biochim. Biophys. Acta 2000, 1458, 482. doi: 10.1016/S0005-2728(00)00096-7(20) Oster, G.; Wang, H. Biochim. Biophys. Acta 2000, 1458, 482. doi: 10.1016/S0005-2728(00)00096-7
27. [27]
  (21) Mrozek, A.; Karolak-Wojciechowska, J.; Kie?-Kononowicz, K. J. Mol. Struct. 2003, 655, 397. doi: 10.1016/S0022-2860(03)00282-5
  (21) Mrozek, A.; Karolak-Wojciechowska, J.; Kie?-Kononowicz, K. J. Mol. Struct. 2003, 655, 397. doi: 10.1016/S0022-2860(03)00282-5

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沈阳化工大学材料科学与工程学院沈阳 110142

分子动力学研究F₁-ATP合酶对三磷酸腺苷的稳定和定位作用

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中国化学会秘书处

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