Citation: Zhang Yu, Yang Xinya, Yu Haiying, Ma Guangcai. Theoretical Insight into the Catalytic Mechanism of Enoyl-CoA Hydratase[J]. Acta Chimica Sinica, ;2017, 75(5): 494-500. doi: 10.6023/A16100559 shu

Theoretical Insight into the Catalytic Mechanism of Enoyl-CoA Hydratase

College of Geography and Environmental Sciences, Zhejiang Normal University, Jinhua 321004, China

Corresponding author: Ma Guangcai, magc@zjnu.edu.cn
Received Date: 20 October 2016

Fund Project: the Natural Science Foundation of Zhejiang Province LY16B070002Technological Innovation Plan & New Talent Plan for College Students in Zhejiang Province 2015R404006

Figures(7)

Enoyl-CoA hydratase (ECH), which is also known as crotonase, is the second requisite enzyme in the β-oxidation pathway of fatty acid that catalyzes the syn hydration of α, β-unsaturated thiolester substrates. In this work, ECH-catalyzed hydration mechanisms of DAC-CoA and Crotonyl-CoA were investigated using density functional theory (DFT) methods. Geometrical structures were optimized using Gaussian 03 program at the B3LYP/6-31G(d, p) level of theory. Frequency calculations were performed with the 6-31G(d, p) basis set to obtain zero-point vibrational energies (ZPEs) and to confirm the nature of all the stationary points that have no imaginary frequency for the local minima and have only one imaginary frequency for the saddle points. The single-point calculations on the optimized geometries were further performed with 6-311++G(2d, 2p) basis set to obtain more accurate energies. The polarizable-continuum model (PCM) with the dielectric constant of 4 was used to calculate the single point energies at 6-311++G(2d, p) level on all the optimized geometries to consider the effects of enzymatic environment that was not included in the computational model. Considering that B3LYP functional lacks the proper description of the long-range dispersion interactions, we further used the DFT-D3 program to calculate the empirical dispersion correction to correct the B3LYP energies. The final energies reported in this work are the single-point energies corrected for ZPEs, solvation and dispersion effects. The calculated results suggested that hydration proceeds through a stepwise mechanism, involving an enolate intermediate. Glu164 functions as the sole base/acid for catalysis. Although Glu144 is not directly involved in hydration, it induces the catalytic water molecule to locate an ideal orientation to attack the double bond of substrate by the hydrogen-bonding interaction. Crotonyl-CoA shows higher hydration activity than DAC-CoA. The backbone NH groups of Ala98 and Gly141 form an oxyanion hole with substrate carbonyl oxygen, which play key roles in binding substrate and stabilizing the generated transition states and intermediates. In addition, the hydrogen-bonding networks surrounding Glu144 and Glu164 are of great importance for active site arrangement.
- Enoyl-CoA hydratase,
- catalytic mechanism,
- density functional theory,
- DAC-CoA,
- Crotonyl-CoA
1. [1]
  Willadsen, P.; Eggerer, H. Eur. J. Biochem. 1975, 54, 247. doi: 10.1111/ejb.1975.54.issue-1
2. [2]
  Wu, W. J.; Feng, Y.; He, X.; Hofstein, H. A.; Raleigh, D. P.; Tonge, P. J. J. Am. Chem. Soc. 2000, 122, 3987. doi: 10.1021/ja992286h
3. [3]
  Bahnson, B. J.; Anderson, V. E. Biochemistry 1989, 28, 4173. doi: 10.1021/bi00436a008
4. [4]
  Müller-Newen, G.; Janssen, U.; Stoffel, W. Eur. J. Biochem. 1995, 228, 68. doi: 10.1111/ejb.1995.228.issue-1
5. [5]
  Boersma, A. J.; Coquière, D.; Geerdink, D.; Rosati, F.; Feringa, B. L.; Roelfes, G. Nat. Chem. 2010, 2, 991. doi: 10.1038/nchem.819
6. [6]
  Silverman, R. B. The Organic Chemistry of Enzyme-catalyzed Reactions, Academic, London, 2002, pp. 428~448.
7. [7]
  Engel, C. K.; Mathieu, M.; Zeelen, J. P.; Hiltunen, J. K.; Wierenga, R. K. EMBO J. 1996, 15, 5135.
8. [8]
  Bahnson, B. J.; Anderson, V. E.; Petsko, G. A. Biochemistry 2002, 41, 2621. doi: 10.1021/bi015844p
9. [9]
  Hisano, T.; Tsuge, T.; Fukui, T.; Iwata, T.; Miki, K.; Doi, Y. J. Biol. Chem. 2003, 278, 617.
10. [10]
  Koski, M. K.; Haapalainen, A. M.; Hiltunen, J. K.; Glumoff, T. J. Biol. Chem. 2004, 279, 24666. doi: 10.1074/jbc.M400293200
11. [11]
  Baugh, L.; Phan, I.; Begley, D. W.; Clifton, M. C.; Armour, B.; Dranow, D. M.; Taylor, B. M.; Muruthi, M. M.; Abendroth, J.; Fairman, J. W.; Fox, D. 3rd; Dieterich, S. H.; Staker, B. L.; Gardberg, A. S.; Choi, R.; Hewitt, S. N.; Napuli, A. J.; Myers, J.; Barrett, L. K.; Zhang, Y.; Ferrell, M.; Mundt, E.; Thompkins, K.; Tran, N.; Lyons-Abbott, S.; Abramov, A.; Sekar, A.; Serbzhinskiy, D, ; Lorimer, D.; Buchko, G. W.; Stacy, R.; Stewart, L. J.; Edwards, T. E.; Van Voorhis, W. C.; Myler, P. J. Tuberculosis 2015, 95, 142.
12. [12]
  Feng, Y.; Hofstein, H. A.; Zwahlen, J.; Tonge, P. J. Biochemistry 2002, 41, 12883. doi: 10.1021/bi020382g
13. [13]
  Hofstein, H. A.; Feng, Y.; Anderson, V. E.; Tonge, P. J. Biochemistry 1999, 38, 9508. doi: 10.1021/bi990506y
14. [14]
  Engel, C. K.; Kiema, T. R.; Hiltunen, J. K.; Wierenga, R. K. J. Mol. Biol. 1998, 275, 847. doi: 10.1006/jmbi.1997.1491
15. [15]
  Bell, A. F.; Wu, J.; Feng, Y.; Tonge, P. J. Biochemistry 2001, 40, 1725. doi: 10.1021/bi001733z
16. [16]
  D'Ordine, R. L.; Pawlak, J.; Bahnson, B. J.; Anderson, V. E.; Biochemistry 2002, 41, 2630. doi: 10.1021/bi015845h
17. [17]
  Bahnson, B. J.; Anderson, V. E. Biochemistry 1991, 30, 5894. doi: 10.1021/bi00238a013
18. [18]
  Pawlak, J.; Bahnson, B.; Anderson, V. Nukleonika 2002, 47, 33.
19. [19]
  Cui, X.; He, R.; Yang, Q.; Shen, W.; Li, M. J. Mol. Model. 2014, 20, 2411. doi: 10.1007/s00894-014-2411-5
20. [20]
  Agnihotri, G.; Liu, H. W. Bioorg. Med. Chem. 2003, 11, 9. doi: 10.1016/S0968-0896(02)00333-4
21. [21]
  Siegbahn, P. E.; Himo, F. J. Biol. Inorg. Chem. 2009, 14, 643. doi: 10.1007/s00775-009-0511-y
22. [22]
  Siegbahn, P. E.; Blomberg, M. R. Chem. Rev. 2010, 110, 7040. doi: 10.1021/cr100070p
23. [23]
  Hopmann, K. H.; Himo, F. In Comprehensive Natural Products Chemistry Ⅱ Chemistry and Biology, Vol. 8, Eds.: Mander, L. N.; Liu, H.-W., Elsevier, Oxford, 2010, pp. 719~747.
24. [24]
  Siegbahn, P. E.; Himo, F. Wiley Interdisciplinary Reviews: Computational Molecular Science, 2011, 1, 323. doi: 10.1002/wcms.13
25. [25]
  Blomberg, M. R.; Borowski, T.; Himo, F.; Liao, R. Z.; Siegbahn, P. E. Chem. Rev. 2014, 114, 3601. doi: 10.1021/cr400388t
26. [26]
  Becke, A. D. J. Chem. Phys. 1993, 98, 5648. doi: 10.1063/1.464913
27. [27]
  Lee, C.; Yang, W.; Parr, R. G. Phys. Rev. B 1988, 37, 785. doi: 10.1103/PhysRevB.37.785
28. [28]
  Frisch, M. J.; Trucks, G. W.; Schlegel, H. B.; Scuseria, G. E.; Robb, M. A.; Cheeseman, J. R.; Montgomery, J. A., Jr.; Vreven, T.; Kudin, K. N.; Burant, J. C.; Millam, J. M.; Iyengar, S. S.; Tomasi, J.; Barone, V.; Mennucci, B.; Cossi, M.; Scalmani, G.; Rega, N.; Petersson, G. A.; Nakatsuji, H.; Hada, M.; Ehara, M.; Toyota, K.; Fukuda, R.; Hasegawa, J.; Ishida, M.; Nakajima, T.; Honda, Y.; Kitao, O.; Nakai, H.; Klene, M.; Li, X.; Knox, J. E.; Hratchian, H. P.; Cross, J. B.; Adamo, C.; Jaramillo, J.; Gomperts, R.; Stratmann, R. E.; Yazyev, O.; Austin, A. J.; Cammi, R.; Pomelli, C.; Ochterski, J. W.; Ayala, P. Y.; Morokuma, K.; Voth, G. A.; Salvador, P.; Dannenberg, J. J.; Zakrzewski, V. G.; Dapprich, S.; Daniels, A. D.; Strain, M. C.; Farkas, O.; Malick, D. K.; Rabuck, A. D.; Raghavachari, K.; Foresman, J. B.; Ortiz, J. V.; Cui, Q.; Baboul, A. G.; Clifford, S.; Cioslowski, J.; Stefanov, B. B.; Liu, G.; Liashenko, A.; Piskorz, P.; Komaromi, I.; Martin, R. L.; Fox, D. J.; Keith, T.; Al-Laham, M. A.; Peng, C. Y.; Nanayakkara, A.; Challacombe, M.; Gill, P. M. W.; Johnson, B.; Chen, W.; Wong, M. W.; Gonzalez, C.; Pople, J. A. Gaussian 03 (Revision D. 01), Gaussian, Inc., Wallingford CT, 2004.
29. [29]
  Barone, V.; Cossi, M.; Tomasi, J. J. Comput. Chem. 1998, 19, 404. doi: 10.1002/(ISSN)1096-987X
30. [30]
  Tomasi, J.; Persico, M. Chem. Rev. 1994, 94, 2027. doi: 10.1021/cr00031a013
31. [31]
  Grimme, S.; Antony, J.; Ehrlich, S.; Krieg, H. J. Chem. Phys. 2010, 132, 154104. doi: 10.1063/1.3382344
32. [32]
  Grimme, S.; Ehrlich, S.; Goerigk, L. J. Comput. Chem. 2011, 32, 1456. doi: 10.1002/jcc.v32.7
33. [33]
  D'Ordine, R. L.; Tonge, P. J.; Carey, P. R.; Anderson, V. E. Biochemistry 1994, 33, 12635. doi: 10.1021/bi00208a014
1. [1]
  Yingchun ZHANG , Yiwei SHI , Ruijie YANG , Xin WANG , Zhiguo SONG , Min WANG . Dual ligands manganese complexes based on benzene sulfonic acid and 2, 2′-bipyridine: Structure and catalytic properties and mechanism in Mannich reaction. Chinese Journal of Inorganic Chemistry, 2024, 40(8): 1501-1510. doi: 10.11862/CJIC.20240078
2. [2]
  Hao XU , Ruopeng LI , Peixia YANG , Anmin LIU , Jie BAI . Regulation mechanism of halogen axial coordination atoms on the oxygen reduction activity of Fe-N₄ site: A density functional theory study. Chinese Journal of Inorganic Chemistry, 2025, 41(4): 695-701. doi: 10.11862/CJIC.20240302
3. [3]
  Lirui Shen , Kun Liu , Ying Yang , Dongwan Li , Wengui Chang . Synthesis and Application of Decanedioic Acid-N-Hydroxysuccinimide Ester: Exploration of Teaching Reform in Comprehensive Applied Chemistry Experiment. University Chemistry, 2024, 39(8): 212-220. doi: 10.3866/PKU.DXHX202312035
4. [4]
  Meifeng Zhu , Jin Cheng , Kai Huang , Cheng Lian , Shouhong Xu , Honglai Liu . Classical Density Functional Theory for Understanding Electrochemical Interface. University Chemistry, 2025, 40(3): 148-152. doi: 10.12461/PKU.DXHX202405166
5. [5]
  Yikai Wang , Xiaolin Jiang , Haoming Song , Nan Wei , Yifan Wang , Xinjun Xu , Cuihong Li , Hao Lu , Yahui Liu , Zhishan Bo . 氰基修饰的苝二酰亚胺衍生物作为膜厚不敏感型阴极界面材料用于高效有机太阳能电池. Acta Physico-Chimica Sinica, 2025, 41(3): 2406007-. doi: 10.3866/PKU.WHXB202406007
6. [6]
  Heng Zhang . Determination of All Rate Constants in the Enzyme Catalyzed Reactions Based on Michaelis-Menten Mechanism. University Chemistry, 2024, 39(4): 395-400. doi: 10.3866/PKU.DXHX202310047
7. [7]
  Jingzhao Cheng , Shiyu Gao , Bei Cheng , Kai Yang , Wang Wang , Shaowen Cao . 4-氨基-1H-咪唑-5-甲腈修饰供体-受体型氮化碳光催化剂的构建及其高效光催化产氢研究. Acta Physico-Chimica Sinica, 2024, 40(11): 2406026-. doi: 10.3866/PKU.WHXB202406026
8. [8]
  Zhiquan Zhang , Baker Rhimi , Zheyang Liu , Min Zhou , Guowei Deng , Wei Wei , Liang Mao , Huaming Li , Zhifeng Jiang . Insights into the Development of Copper-based Photocatalysts for CO₂ Conversion. Acta Physico-Chimica Sinica, 2024, 40(12): 2406029-. doi: 10.3866/PKU.WHXB202406029
9. [9]
  Jingjie Tang , Luying Xie , Jiayu Liu , Shangyu Shi , Xinyu Sun , Jiayang Lin , Qikun Yang , Chuan'ang Yu , Zecheng Wang , Yingying Wang , Zengyang Xie . Efficient Rapid Synthesis and Antibacterial Activities of Tosylhydrazones: A Recommended Innovative Chemistry Experiment for Undergraduate Medical University. University Chemistry, 2024, 39(3): 316-326. doi: 10.3866/PKU.DXHX202309091
10. [10]
  Yanglin Jiang , Mingqing Chen , Min Liang , Yige Yao , Yan Zhang , Peng Wang , Jianping Zhang . Experimental and Theoretical Investigations of Solvent Polarity Effect on ESIPT Mechanism in 4′-N,N-diethylamino-3-hydroxybenzoflavone. Acta Physico-Chimica Sinica, 2025, 41(2): 100012-. doi: 10.3866/PKU.WHXB202309027
11. [11]
  Guoqiang Chen , Zixuan Zheng , Wei Zhong , Guohong Wang , Xinhe Wu . 熔融中间体运输导向合成富氨基g-C₃N₄纳米片用于高效光催化产H₂O₂. Acta Physico-Chimica Sinica, 2024, 40(11): 2406021-. doi: 10.3866/PKU.WHXB202406021
12. [12]
  Tianlong Zhang , Rongling Zhang , Hongsheng Tang , Yan Li , Hua Li . Online Monitoring and Mechanistic Analysis of 3,5-diamino-1,2,4-triazole (DAT) Synthesis via Raman Spectroscopy: A Recommendation for a Comprehensive Instrumental Analysis Experiment. University Chemistry, 2024, 39(6): 303-311. doi: 10.3866/PKU.DXHX202312006
13. [13]
  Yinuo Wang , Siran Wang , Yilong Zhao , Dazhen Xu . Selective Synthesis of Diarylmethyl Anilines and Triarylmethanes via Multicomponent Reactions: Introduce a Comprehensive Experiment of Organic Chemistry. University Chemistry, 2024, 39(8): 324-330. doi: 10.3866/PKU.DXHX202401063
14. [14]
  Xiao SANG , Qi LIU , Jianping LANG . Synthesis, structure, and fluorescence properties of Zn(Ⅱ) coordination polymers containing tetra-alkenylpyridine ligands. Chinese Journal of Inorganic Chemistry, 2024, 40(11): 2124-2132. doi: 10.11862/CJIC.20240158
15. [15]
  Yi DING , Peiyu LIAO , Jianhua JIA , Mingliang TONG . Structure and photoluminescence modulation of silver(Ⅰ)-tetra(pyridin-4-yl)ethene metal-organic frameworks by substituted benzoates. Chinese Journal of Inorganic Chemistry, 2025, 41(1): 141-148. doi: 10.11862/CJIC.20240393
16. [16]
  Yuanyin Cui , Jinfeng Zhang , Hailiang Chu , Lixian Sun , Kai Dai . Rational Design of Bismuth Based Photocatalysts for Solar Energy Conversion. Acta Physico-Chimica Sinica, 2024, 40(12): 2405016-. doi: 10.3866/PKU.WHXB202405016
17. [17]
  Dan Li , Hui Xin , Xiaofeng Yi . Comprehensive Experimental Design on Ni-based Catalyst for Biofuel Production. University Chemistry, 2024, 39(8): 204-211. doi: 10.3866/PKU.DXHX202312046
18. [18]
  Min LIU , Huapeng RUAN , Zhongtao FENG , Xue DONG , Haiyan CUI , Xinping WANG . Neutral boron-containing radical dimers. Chinese Journal of Inorganic Chemistry, 2025, 41(1): 123-130. doi: 10.11862/CJIC.20240362
19. [19]
  Wen YANG , Didi WANG , Ziyi HUANG , Yaping ZHOU , Yanyan FENG . La promoted hydrotalcite derived Ni-based catalysts: In situ preparation and CO₂ methanation performance. Chinese Journal of Inorganic Chemistry, 2024, 40(3): 561-570. doi: 10.11862/CJIC.20230276
20. [20]
  .
  CCS Chemistry | 超分子活化底物为自由基促进高效选择性光催化氧化
  . CCS Chemistry, 2025, 7(10.31635/ccschem.025.202405229): -.

Get Citation

PDF

XML

Metrics

PDF Downloads(28)
Abstract views(2249)
HTML views(728)

通讯作者: 陈斌, bchen63@163.com

1.
沈阳化工大学材料科学与工程学院沈阳 110142