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New insights into the mechanism of the Schiff base formation catalyzed by type I dehydroquinate dehydratase from S. enterica

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Abstract

The Schiff base formation catalyzed by type I dehydroquinate dehydratase (DHQD) from Salmonella enterica has been studied by molecular docking, molecular dynamics simulation, and quantum chemical calculations. The substrate locates stably a similar position as the Schiff base intermediate observed in the crystal structure and forms strong hydrogen bonds with several active site residues. This binding mode is different from that of several other Schiff base enzymes. Then, the quantum chemical model has been constructed and the fundamental reaction pathways have been explored by performing quantum chemical calculation. The energy barrier of the previously proposed reaction pathway is calculated to be 30.7 kcal/mol, which is much higher than the experimental value of 14.3 kcal/mol of the whole dehydration reaction by type I DHQD from S. enterica. It means that this pathway is not favorable in energy. Therefore, a new and unexpected reaction pathway has been investigated with the favorable and reasonable energy barrier of 12.1 kcal/mol. The complicated role of catalytic His143 residue has also been elucidated that it mediates two proton transfers to facilitate the reaction. Moreover, the similarity and the difference between these two reaction pathways have been analyzed in detail. The new structural and mechanistic insights may direct the design of the inhibitors of type I dehydroquinate dehydratase as non-toxic antimicrobials, antifungals, and herbicides.

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References

  1. Bentley R (1990) Crit Rev Biochem Mol Biol 25:307–384

    Article  CAS  Google Scholar 

  2. Marques MR, Pereira JH, Oliveira JS, Basso LA, de Azevedo WF, Santos DS, Palma MS (2007) Curr Drug Targets 8(3):445–457

    Article  CAS  Google Scholar 

  3. Noble M, Sinha Y, Kolupaev A, Demin O, Earnshaw D, Tobin F, West J, Martin JD, Qiu CY, Liu WS, DeWolf WE, Tew D, Goryanin II (2006) Biotechnol Bioeng 95(4):560–573. doi:10.1002/Bit.20772

    Article  CAS  Google Scholar 

  4. Butler JR, Alworth WL, Nugent MJ (1974) J Am Chem Soc 96(5):1617–1618

    Article  CAS  Google Scholar 

  5. Gourley DG, Shrive AK, Polikarpov I, Krell T, Coggins JR, Hawkins AR, Isaacs NW, Sawyer L (1999) Nat Struct Biol 6(6):521–525

    Article  CAS  Google Scholar 

  6. Kleanthous C, Deka R, Davis K, Kelly SM, Cooper A, Harding SE, Price NC, Hawkins AR, Coggins JR (1992) Biochem J 282:687–695

    CAS  Google Scholar 

  7. White PJ, Young J, Hunter IS, Nimmo HG, Coggins JR (1990) Biochem J 265(3):735–738

    CAS  Google Scholar 

  8. Harris J, Kleanthous C, Coggins JR, Hawkins AR, Abell C (1993) Chem Commun 13:1080–1081

    Google Scholar 

  9. Leech AP, James R, Coggins JR, Kleanthous C (1995) J Biol Chem 270(43):25827–25836

    Article  CAS  Google Scholar 

  10. Light SH, Minasov G, Shuvalova L, Duban ME, Caffrey M, Anderson WF, Lavie A (2011) J Biol Chem 286(5):3531–3539

    Article  CAS  Google Scholar 

  11. Burgi HB, Dunitz JD, Lehn JM, Wipff G (1974) Tetrahedron 30(12):1563–1572

    Article  Google Scholar 

  12. Blom N, Sygusch J (1997) Nat Struct Biol 4(1):36–39

    Article  CAS  Google Scholar 

  13. Soares da Costa TP, Muscroft-Taylor AC, Dobson RCJ, Devenish SRA, Jameson GB, Gerrard JA (2010) Biochimie 92(7):837–845

    Google Scholar 

  14. Pohl E, Pauluhn A, Ahmed H, Lorentzen E, Buchinger S, Schomburg D, Siebers B (2008) Proteins 72(1):35–43

    Article  Google Scholar 

  15. Chaudhuri S, Lambert JM, Mccoll LA, Coggins JR (1986) Biochem J 239(3):699–704

    CAS  Google Scholar 

  16. Deka RK, Kleanthous C, Coggins JR (1992) J Biol Chem 267(31):22237–22242

    CAS  Google Scholar 

  17. Leech AP, Boetzel R, McDonald C, Shrive AK, Moore GR, Coggins JR, Sawyer L, Kleanthous C (1998) J Biol Chem 273(16):9602–9607

    Article  CAS  Google Scholar 

  18. Li H, Robertson AD, Jensen JH (2005) Proteins 61(4):704–721

    Article  CAS  Google Scholar 

  19. Bas DC, Rogers DM, Jensen JH (2008) Proteins 73(3):765–783

    Article  CAS  Google Scholar 

  20. Olsson MHM, Søndergaard CR, Rostkowski M, Jensen JH (2011) J Chem Theory Comput 7(2):525–537

    Article  CAS  Google Scholar 

  21. Søndergaard CR, Olsson MHM, Rostkowski M, Jensen JH (2011) J Chem Theory Comput 7(7):2284–2295

    Article  Google Scholar 

  22. Morris GM, Huey R, Lindstrom W, Sanner MF, Belew RK, Goodsell DS, Olson AJ (2009) J Comput Chem 30(16):2785–2791

    Article  CAS  Google Scholar 

  23. Case DA, Cheatham TE, Darden T, Gohlke H, Luo R, Merz KM, Onufriev A, Simmerling C, Wang B, Woods RJ (2005) J Comput Chem 26(16):1668–1688

    Article  CAS  Google Scholar 

  24. Case Dad TA, Cheatham TE, Simmerling CL, Wang J, Duke RE, Luo R, Merz KM, Pearlman DA, Crowley M, Walker RC, Zhang W, Wang B, Hayik S, Roitberg A, Seabra G, Wong KF, Paesani F, Wu X, Brozell S, Tsui V, Gohlke H, Yang L, Tan C, Mongan J, Hornak V, Cui G, Beroza P, Mathews DH, Schafmeister C, Ross WS, Kollman PA (2006) Amber 9. University of California, San Francisco

  25. Jorgensen WL, Chandrasekhar J, Madura JD, Impey RW, Klein ML (1983) J Chem Phys 79(2):926–935

    Article  CAS  Google Scholar 

  26. Miyamoto S, Kollman PA (1992) J Comput Chem 13(8):952–962

    Article  CAS  Google Scholar 

  27. Ryckaert JP, Ciccotti G, Berendsen HJC (1977) J Comput Phys 23(3):327–341

    Article  CAS  Google Scholar 

  28. Frisch MJT, G. W, Schlegel HB, Scuseria GE, Robb MA, Cheeseman JR, Montgomery JJA, Vreven T, Kudin KN, Burant JC, Millam JM, Iyengar SS, Tomasi J, Barone V, Mennucci B, Cossi M, Scalmani G, Rega N, Petersson GA, 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 JE, Hratchian HP, Cross JB, Bakken V, Adamo C, Jaramillo J, Gomperts R, Stratmann RE, Yazyev O, Austin AJ, Cammi R, Pomelli C, Ochterski JW, Ayala PY, Morokuma K, Voth GA, Salvador P, Dannenberg JJ, Zakrzewski VG, Dapprich S, Daniels AD, Strain MC, Farkas O, Malick DK, Rabuck AD, Raghavachari K, Foresman JB, Ortiz JV, Cui Q, Baboul AG, Clifford S, Cioslowski J, Stefanov BB, Liu G, Liashenko A, Piskorz P, Komaromi I, Martin RL, Fox DJ, Keith T, Al-Laham MA, Peng CY, Nanayakkara A, Challacombe M, Gill PMW, Johnson B, Chen W, Wong MW, Gonzalez C, Pople JA (2004) Gaussian 03, Revision E01. Gaussian, Inc., Wallingford CT

  29. Cossi M, Barone V, Cammi R, Tomasi J (1996) Chem Phys Lett 255(4–6):327–335

    Article  CAS  Google Scholar 

  30. Miertus S, Scrocco E, Tomasi J (1981) Chem Phys 55(1):117–129

    Article  CAS  Google Scholar 

  31. Miertus S, Tomasi J (1982) Chem Phys 65(2):239–245

    Article  CAS  Google Scholar 

  32. Noodleman L, Lovell T, Han WG, Li J, Himo F (2004) Chem Rev 104(2):459–508

    Article  CAS  Google Scholar 

  33. Cui FC, Pan XL, Liu W, Liu JY (2011) J Comput Chem 32:3068–3074

    Article  CAS  Google Scholar 

  34. Himo F, Eriksson LA, Maseras F, Seigbahn PEM (2000) J Am Chem Soc 122:8031–8036

    Article  CAS  Google Scholar 

  35. Cui FC, Pan XL, Liu JY (2010) J Phys Chem B 114(29):9622–9628

    Article  CAS  Google Scholar 

  36. Himo F, Chen SL, Marino T, Fang WH, Russo N (2008) J Phys Chem B 112(8):2494–2500

    Article  Google Scholar 

  37. Himo F, Liao RZ, Yu JG (2010) Proc Natl Acad Sci USA 107(52):22523–22527

    Article  Google Scholar 

  38. Himo F, Liao RZ, Yu JG (2010) J Phys Chem B 114(7):2533–2540

    Article  Google Scholar 

  39. Liao RZ, Yu JG, Himo F (2011) J Chem Theory Comput 7(5):1494–1501

    Article  CAS  Google Scholar 

  40. Highbarger LA, Gerlt JA, Kenyon GL (1996) Biochemistry 35(1):41–46

    Article  CAS  Google Scholar 

  41. Reed AE, Weinhold F (1985) J Chem Phys 83(4):1736–1740

    Article  CAS  Google Scholar 

  42. Reed AE, Weinstock RB, Weinhold F (1985) J Chem Phys 83(2):735–746

    Article  CAS  Google Scholar 

Download references

Acknowledgments

This work was supported by the Major State Basic Research Development Programs of China (2011CBA00701), the National Natural Science Foundation of China (20973049), and Development Program for Outstanding Young Teachers in Harbin Institute of Technology (HITQNJS.2009.069).

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Authors and Affiliations

  1. Academy of Fundamental and Interdisciplinary Science, Harbin Institute of Technology, Harbin, 150080, People’s Republic of China

    Qi Pan, Yuan Yao & Ze-Sheng Li

  2. Department of Orthopaedic, The First Affiliated Hospital of Harbin Medical University, Harbin, 150080, People’s Republic of China

    Qi Pan

  3. Key Laboratory of Cluster Science of Ministry of Education, School of Chemistry, Beijing Institute of Technology, No. 5 Yard, Zhong Guan Cun South Street, Beijing, 100081, People’s Republic of China

    Ze-Sheng Li

Authors
  1. Qi Pan
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  2. Yuan Yao
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Correspondence to Yuan Yao or Ze-Sheng Li.

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Pan, Q., Yao, Y. & Li, ZS. New insights into the mechanism of the Schiff base formation catalyzed by type I dehydroquinate dehydratase from S. enterica . Theor Chem Acc 131, 1204 (2012). https://doi.org/10.1007/s00214-012-1204-0

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