Citation: Xiaoning Wang, Hongyan Lin, Junjun Liu, Xinyun Zhao, Xi Chen, Wenchao Yang, Guangfu Yang, Chang-guo Zhan. The structure of 4-hydroxylphenylpyruvate dioxygenase complexed with 4-hydroxylphenylpyruvic acid reveals an unexpected inhibition mechanism[J]. Chinese Chemical Letters, ;2021, 32(6): 1920-1924. doi: 10.1016/j.cclet.2021.02.041 shu

The structure of 4-hydroxylphenylpyruvate dioxygenase complexed with 4-hydroxylphenylpyruvic acid reveals an unexpected inhibition mechanism

Xiaoning Wang ^{a, 1} ,
Hongyan Lin ^{b, 1} ,
Junjun Liu ^c ,
Xinyun Zhao ^a ,
Xi Chen ^{a, *,} ,
Wenchao Yang ^{b, *,} ,
Guangfu Yang ^{b, *,} ,
Chang-guo Zhan ^d

a.
College of Chemistry and Material Science, South-Central University for Nationalities, Wuhan 430074, China
b.
Key Laboratory of Pesticide & Chemical Biology of Ministry of Education, College of Chemistry, Central China Normal University, Wuhan 430079, China
c.
School of Pharmacy, Tongji Medical College of Huazhong University of Science & Technology, Wuhan 430030, China
d.
Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, KY 40536, United States

chen@mail.scuec.edu.cn

tomyang@mail.ccnu.edu.cn

gfyang@mail.ccnu.edu.cn

Received Date: 16 January 2021
Revised Date: 17 February 2021
Accepted Date: 18 February 2021
Available Online: 22 February 2021

Figures(6)

4-Hydroxyphenylpyruvate dioxygenase (HPPD) is an important target for both drug and pesticide discovery. As a typical Fe(Ⅱ)-dependent dioxygenase, HPPD catalyzes the complicated transformation of 4-hydroxyphenylpyruvic acid (HPPA) to homogentisic acid (HGA). The binding mode of HPPA in the catalytic pocket of HPPD is a focus of research interests. Recently, we reported the crystal structure of Arabidopsis thaliana HPPD (AtHPPD) complexed with HPPA and a cobalt ion, which was supposed to mimic the pre-reactive structure of AtHPPD-HPPA-Fe(Ⅱ). Unexpectedly, the present study shows that the restored AtHPPD-HPPA-Fe(Ⅱ) complex is still nonreactive toward the bound dioxygen. QM/MM and QM calculations reveal that the HPPA resists the electrophilic attacking of the bound dioxygen by the trim of its phenyl ring, and the residue Phe381 plays a key role in orienting the phenyl ring. Kinetic study on the F381A mutant reveals that the HPPD-HPPA complex observed in the crystal structure should be an intermediate of the substrate transportation instead of the pre-reactive complex. More importantly, the binding mode of the HPPA in this complex is shared with several well-known HPPD inhibitors, suggesting that these inhibitors resist the association of dioxygen (and exert their inhibitory roles) in the same way as the HPPA. The present study provides insights into the inhibition mechanism of HPPD inhibitors.
- 4-Hydroxyphenylpyruvate dioxygenase,
- QM/MM calculation,
- Potential surface scan,
- Substrate self-inhibition
1. [1]
  N.P. Crouch, M.H. Lee, T. Iturriagagoitia-Bueno, et al., Cloning, Expression, and Purification of Mammalian 4-Hydroxyphenylpyruvate Dioxygenase/α-Ketoisocaproate Dioxygenase, Academic Press, Salt Lake City, 2000.
2. [2]
  M. Kohlmeier, Amino Acids and Nitrogen Compounds, Academic Press, San Diego, 2015.
3. [3]
  H. Ahrens, G. Lange, T. Muller, et al., Angew. Chem. Int. Ed. Eng. 52(2013) 9388-9398. doi: 10.1002/anie.201302365
4. [4]
  R. Beaudegnies, A.J. Edmunds, T.E. Fraser, et al., Bioorg. Med. Chem. 17(2009) 4134-4152. doi: 10.1016/j.bmc.2009.03.015
5. [5]
  D.W. Wang, H.Y. Lin, B. He, et al., J. Agric. Food Chem. 64(2016) 8986-8993. doi: 10.1021/acs.jafc.6b04110
6. [6]
  D.C. Bartlett, C. Lloyd, P.J. McKiernan, et al., J. Inherit. Metab. Dis. 37(2014) 745-752. doi: 10.1007/s10545-014-9683-x
7. [7]
  D.D. Shah, J.A. Conrad, B. Heinz, et al., Biochemistry 50(2011) 7694-7704. doi: 10.1021/bi2009344
8. [8]
  D.D. Shah, J.A. Conrad, G.R. Moran, Biochemistry 52(2013) 6097-6107. doi: 10.1021/bi400534q
9. [9]
  T. Borowski, A. Bassan, P.E. Siegbahn, Biochemistry 43(2004) 12331-12342. doi: 10.1021/bi049503y
10. [10]
  C. Raspail, M. Graindorge, Y. Moreau, et al., J. Biol. Chem. 286(2011) 26061-26070. doi: 10.1074/jbc.M111.227595
11. [11]
  A. Wójcik, E. Broclawik, P.E.M. Siegbahn, et al., J. Am. Chem. Soc. 136(2014) 14472-14485. doi: 10.1021/ja506378u
12. [12]
  H.Y. Lin, X. Chen, J.N. Chen, et al., Research 2019(2019) 2602414.
13. [13]
  J.F. Lin, Y.L. Sheih, T.C. Chang, et al., PLoS One 8(2013) e69733. doi: 10.1371/journal.pone.0069733
14. [14]
  M. Gunsior, J. Ravel, G.L. Challis, et al., Biochemistry 43(2004) 663-674. doi: 10.1021/bi035762w
15. [15]
  T. Borowski, M. Quesne, M. Szaleniec, QM and QM/MM methods compared: case studies on reaction mechanisms of metalloenzymes, in: T. KarabenchevaChristova (Ed.), Advances in Protein Chemistry and Structural Biology, Academic Press, Salt Lake City, 2015.
16. [16]
  K. Johnson-Winters, V.M. Purpero, M. Kavana, et al., Biochemistry 42(2003) 2072-2080. doi: 10.1021/bi026499m
17. [17]
  G.R. Moran, Arch. Biochem. Biophys. 544(2014) 58-68. doi: 10.1016/j.abb.2013.10.022
18. [18]
  C. Yang, J.W. Pflugrath, D.L. Camper, et al., Biochemistry 43(2004) 10414-10423. doi: 10.1021/bi049323o
19. [19]
  I.M. Fritze, L. Linden, J. Freigang, et al., Plant Physiol. 134(2004) 1388-1400. doi: 10.1104/pp.103.034082
20. [20]
  J.M. Brownlee, K. Johnson-Winters, D.H.T. Harrison, et al., Biochemistry 43(2004) 6370-6377. doi: 10.1021/bi049317s
21. [21]
  I.M. Fritze, L. Linden, J. Freigang, et al., Plant Physiol. 134(2004) 1388-1400. doi: 10.1104/pp.103.034082
22. [22]
  J. Brownlee, P. He, G.R. Moran, et al., Biochemistry 47(2008) 2002-2013. doi: 10.1021/bi701438r
23. [23]
  A. Wójcik, M. Radon, T. Borowski, J. Phys. Chem. A 120(2016) 1261-1274. doi: 10.1021/acs.jpca.5b12311
24. [24]
  T. Borowski, A. Bassan, P.E.M. Siegbahn, Chem. Eur. J. 10(2004) 1031-1041. doi: 10.1002/chem.200305306
25. [25]
  S. Ye, C. Riplinger, A. Hansen, et al., Chemistry 18(2012) 6555-6567. doi: 10.1002/chem.201102829
26. [26]
  M.M. Mbughuni, M. Chakrabarti, J.A. Hayden, et al., Proc. Natl. Acad. Sci. U. S. A. 107(2010) 16788-16793. doi: 10.1073/pnas.1010015107
27. [27]
  J.C. Price, E.W. Barr, B. Tirupati, et al., Biochemistry 42(2003) 7497-7508. doi: 10.1021/bi030011f
28. [28]
  H.Y. Lin, J.F. Yang, D.W. Wang, et al., FEBS J. 286(2019) 975-990. doi: 10.1111/febs.14747
1. [1]
  Chunyan Yang , Qiuyu Rong , Fengyin Shi , Menghan Cao , Guie Li , Yanjun Xin , Wen Zhang , Guangshan Zhang . Rationally designed S-scheme heterojunction of BiOCl/g-C₃N₄ for photodegradation of sulfamerazine: Mechanism insights, degradation pathways and DFT calculation. Chinese Chemical Letters, 2024, 35(12): 109767-. doi: 10.1016/j.cclet.2024.109767
2. [2]
  Bing Niu , Honggao Huang , Liwei Luo , Li Zhang , Jianbo Tan . Coating colloidal particles with a well-defined polymer layer by surface-initiated photoinduced polymerization-induced self-assembly and the subsequent seeded polymerization. Chinese Chemical Letters, 2025, 36(2): 110431-. doi: 10.1016/j.cclet.2024.110431
3. [3]
  Dan-Ying Xing , Xiao-Dan Zhao , Chuan-Shu He , Bo Lai . Kinetic study and DFT calculation on the tetracycline abatement by peracetic acid. Chinese Chemical Letters, 2024, 35(9): 109436-. doi: 10.1016/j.cclet.2023.109436
4. [4]
  Xiumei LI , Yanju HUANG , Bo LIU , Yaru PAN . Syntheses, crystal structures, and quantum chemistry calculation of two Ni(Ⅱ) coordination polymers. Chinese Journal of Inorganic Chemistry, 2024, 40(10): 2031-2039. doi: 10.11862/CJIC.20240109
5. [5]
  Xiaofei NIU , Ke WANG , Fengyan SONG , Shuyan YU . Self-assembly of [Pd₆(L)₄]⁸⁺-type macrocyclic complexes for fluorescent sensing of HSO₃^-. Chinese Journal of Inorganic Chemistry, 2024, 40(7): 1233-1242. doi: 10.11862/CJIC.20240057
6. [6]
  Zhongchao Zhou , Jian Song , Yinghao Xie , Yuqian Ma , Hong Hu , Hui Li , Lei Zhang , Charles H. Lawrie . DFT calculation for organic semiconductor-based gas sensors: Sensing mechanism, dynamic response and sensing materials. Chinese Chemical Letters, 2025, 36(6): 110906-. doi: 10.1016/j.cclet.2025.110906
7. [7]
  Lili Wang , Xujie Han , Baichuan Xiong , Ya Yan , Cheng Zhang , Yuning Qu , Yiran Zhang , Linlin Zheng , Zirui Gao , Shuheng Tian , Wenjing Dai , Bowen Cheng , Hang Zhang , Zhen Yin . 1D self-supporting NiFe₂O₄/NiMoO₄ heterostructure as bifunctional electrocatalyst via interface engineering for highly efficient seawater splitting. Chinese Chemical Letters, 2025, 36(12): 111437-. doi: 10.1016/j.cclet.2025.111437
8. [8]
  Wenling Yuan , Fengli Li , Zhe Chen , Qiaoxin Xu , Zhenhua Guan , Nanyu Yao , Zhengxi Hu , Junjun Liu , Yuan Zhou , Ying Ye , Yonghui Zhang . AbnI: An α-ketoglutarate-dependent dioxygenase involved in brassicicene CH functionalization and ring system rearrangement. Chinese Chemical Letters, 2024, 35(5): 108788-. doi: 10.1016/j.cclet.2023.108788
9. [9]
  Bingwei Wang , Yihong Ding , Xiao Tian . Benchmarking model chemistry composite calculations for vertical ionization potential of molecular systems. Chinese Chemical Letters, 2025, 36(2): 109721-. doi: 10.1016/j.cclet.2024.109721
10. [10]
  Yinghui Xia , Yixi Lin , Zhenming Xu . Cation potential guiding structural regulation of lithium halide superionic conductors. Chinese Journal of Structural Chemistry, 2025, 44(3): 100448-100448. doi: 10.1016/j.cjsc.2024.100448
11. [11]
  Changxing Yang , Guxia Wang , Shengwei Guo , Jianlin Sun . Potential and progress of two-dimensional nanomaterials in oil-based lubrication. Chinese Chemical Letters, 2025, 36(9): 111178-. doi: 10.1016/j.cclet.2025.111178
12. [12]
  Maitri Bhattacharjee , Rekha Boruah Smriti , R. N. Dutta Purkayastha , Waldemar Maniukiewicz , Shubhamoy Chowdhury , Debasish Maiti , Tamanna Akhtar . Synthesis, structural characterization, bio-activity, and density functional theory calculation on Cu(Ⅱ) complexes with hydrazone-based Schiff base ligands. Chinese Journal of Inorganic Chemistry, 2024, 40(7): 1409-1422. doi: 10.11862/CJIC.20240007
13. [13]
  Yi Zhou , Wei Zhang , Rong Fu , Jiaxin Dong , Yuxuan Liu , Zihang Song , Han Han , Kang Cai . Self-assembly of two pairs of homochiral M₂L₄ coordination capsules with varied confined space using Tröger's base ligands. Chinese Chemical Letters, 2025, 36(2): 109865-. doi: 10.1016/j.cclet.2024.109865
14. [14]
  Fanxin Kong , Hongzhi Wang , Huimei Duan . Inhibition effect of sulfation on Pt/TiO2 catalysts in methane combustion. Chinese Journal of Structural Chemistry, 2024, 43(5): 100287-100287. doi: 10.1016/j.cjsc.2024.100287
15. [15]
  Zhichao Zhou , Fuqian Chen , Xiaotong Xia , Dong Ye , Rong Zhou , Lei Li , Tao Deng , Zhenhua Ding , Fang Liu . Developing a fluorescence substrate for HRP-based diagnostic assays with superiorities over the commercial ADHP. Chinese Chemical Letters, 2024, 35(6): 108970-. doi: 10.1016/j.cclet.2023.108970
16. [16]
  Siyu Cao , Yufei Shu , Li Wang , Qi Han , Meng Zhang , Mengxia Wang , How Yong Ng , Zhongying Wang . Controlling nanomaterial distribution and aggregation in thin-film nanocomposite membranes: Role of substrate pore's relative size with nanomaterials. Chinese Chemical Letters, 2025, 36(10): 110793-. doi: 10.1016/j.cclet.2024.110793
17. [17]
  Kexin Yuan , Yulei Liu , Haoran Feng , Yi Liu , Jun Cheng , Beiyang Luo , Qinglian Wu , Xinyu Zhang , Ying Wang , Xian Bao , Wanqian Guo , Jun Ma . Unlocking the potential of thin-film composite reverse osmosis membrane performance: Insights from mass transfer modeling. Chinese Chemical Letters, 2024, 35(5): 109022-. doi: 10.1016/j.cclet.2023.109022
18. [18]
  Yanjing Li , Jiayin Li , Yuqi Chang , Yunfeng Lin , Lei Sui . Tetrahedral framework nucleic acids promote the proliferation and differentiation potential of diabetic bone marrow mesenchymal stem cell. Chinese Chemical Letters, 2024, 35(9): 109414-. doi: 10.1016/j.cclet.2023.109414
19. [19]
  Jia Chen , Yun Liu , Zerong Long , Yan Li , Hongdeng Qiu . Colorimetric detection of α-glucosidase activity using Ni-CeO₂ nanorods and its application to potential natural inhibitor screening. Chinese Chemical Letters, 2024, 35(9): 109463-. doi: 10.1016/j.cclet.2023.109463
20. [20]
  Ting Li , Xinxin Zheng , Lejing Qu , Yuanyuan Ou , Sai Qiao , Xue Zhao , Yajun Zhang , Xinfeng Zhao , Qian Li . A chromatographic method for pursuing potential GPCR ligands with the capacity to characterize their intrinsic activities of regulating downstream signaling pathway. Chinese Chemical Letters, 2024, 35(10): 109792-. doi: 10.1016/j.cclet.2024.109792

Get Citation

PDF

XML

Metrics

PDF Downloads(7)
Abstract views(1436)
HTML views(101)

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