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Phylogenetic analysis, homology modelling, molecular dynamics and docking studies of caffeoyl–CoA-O- methyl transferase (CCoAOMT 1 and 2) isoforms isolated from subabul (Leucaena leucocephala)

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Abstract

Caffeoyl coenzyme A O-methyltransferase (CCoAOMT) is an important enzyme that participates in lignin biosynthesis especially in the formation of cell wall ferulic esters of plants. It plays a pivotal role in the methylation of the 3-hydroxyl group of caffeoyl CoA. Two cDNA clones that code CCoAOMT were isolated earlier from subabul and in the present study; 3D models of CCoAOMT1 and CCoAOMT2 enzymes were built using the MODELLER7v7 software to find out the substrate binding sites. These two proteins differed only in two amino acids and may have little or no functional redundancy. Refined models of the proteins were obtained after energy minimization and molecular dynamics in a solvated water layer. The models were further assessed by PROCHECK, WHATCHECK, Verify_3D and ERRAT programs and the results indicated that these models are reliable for further active site and docking analysis. The refined models showed that the two proteins have 9 and 10 α-helices, 6 and 7 β-sheets respectively. The models were used for docking the substrates CoA, SAM, SAH, caffeoyl CoA, feruloyl CoA, 5-hydroxy feruloyl CoA and sinapyl CoA which showed that CoA and caffeoyl CoA are binding with high affinity with the enzymes in the presence and absence of SAM. It appears therefore that caffeoyl CoA is the substrate for both the isoenzymes. The results also indicated that CoA and caffeoyl CoA are binding with higher affinity to CCoAOMT2 than CCoAOMT1. Therefore, CCoAOMT2 conformation is thought to be the active form that exists in subabul. Docking studies indicated that conserved active site residues Met58, Thr60, Val63, Glu82, Gly84, Ser90, Asp160, Asp162, Thr169, Asn191 and Arg203 in CCoAOMT1 and CCoAOMT2 enzymes create the positive charge to balance the negatively charged caffeoyl CoA and play an important role in maintaining a functional conformation and are directly involved in donor-substrate binding.

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References

  1. Higuchi T (1998) Kung S-D, Yang S-F (eds) Discoveries in plant biology. World Scientific, Singapore, 233–269

  2. Grima-Pettenati J, Goffner D (1999) Plant Sci 145:51–65

    Article  CAS  Google Scholar 

  3. Meyer K, Sirley AM, Cusumano JC, Bell D Lelong A, Chappel C (1998) Proc Natl Acad Sci USA 95:6619–6623

    Article  CAS  Google Scholar 

  4. Tsai CJ, Mielke MR, Hu WJ, Podila GK, Chiang VL (1998) Plant Physiol 117:101–112

    Article  CAS  Google Scholar 

  5. Zhong R, Morrison WH, Negrel J, Ye ZH (1998) Plant Cell 10:2033–2045

    Article  CAS  Google Scholar 

  6. Ye ZH, Kneusel RE, Matern U, Varner JE (1994) Plant Cell 6:1427–1439

    Article  CAS  Google Scholar 

  7. Ye ZH, Varner JE (1995) Plant Physiol 108:459–467

    Article  CAS  Google Scholar 

  8. Ye ZH (1997) Plant Physiol 115:1341–1350

    Article  CAS  Google Scholar 

  9. Inoue K, Vincent JH, Sewalt G, Balance MNIW, Sturzer C, Dixon RA (1998) Plant Physiol 117:761–770

    Article  CAS  Google Scholar 

  10. Martz F, Maury S, Pincon G, Legrand M (1998) Plant Mol Biol 36:427–437

    Article  CAS  Google Scholar 

  11. Kersey R, Inoue K, Schubert KR, Dixon RA (1999) Protoplasma 209:46–57

    Article  CAS  Google Scholar 

  12. Li L, Osakabe K, Joshi CP, Chiang VL (1999) Plant Mol Biol 40:555–565

    Article  CAS  Google Scholar 

  13. Meng H, Campbell WH (1998) Plant Mol Biol 38:513–520

    Article  CAS  Google Scholar 

  14. Maury S, Geoffroy P, Legrand M (1999) Plant Physiol 121:215–224

    Article  CAS  Google Scholar 

  15. Thompson JD, Gibson TJ, Plewniak F, Jeanmougin F, Higgins DJ (1997) Nucleic Acids Res 24:4876–4882

    Article  Google Scholar 

  16. Nicholas KB, Nicholas HB (1997) http://www.psc.edu/biomed/genedoc [Online.]

  17. Page RDM (1996) Comput Appl Biosci 12:357–358

    CAS  Google Scholar 

  18. Perrière G, Gouy M (1996) Biochimie 78:364–369

    Article  Google Scholar 

  19. Altschul SF, Gish W, Miller W, Myers EW, Lipman DJ (1990) J Mol Biol 215:403–410

    CAS  Google Scholar 

  20. Ferrer J, Zubeita C, Dixon RA, Noel JP (2005) Plant Physiol 137:1009–1017

    Article  CAS  Google Scholar 

  21. Needleman SB, Wunsch CD (1970) J Mol Biol 48:443–453

    Article  CAS  Google Scholar 

  22. Sali A, Blundell TL (1993) J Mol Biol 234:779–815

    Article  CAS  Google Scholar 

  23. MacKerell AD Jr, Bashford D, Bellott M, Dunbrack RL Jr, Evanseck J, Field M, Fischer JS, Gao J, Guo H, Ha S (1998) J Phys Chem B 102:3586–3616

    Article  CAS  Google Scholar 

  24. Sali A, Overington JP (1994) Protein Sci 3:1582–1596

    CAS  Google Scholar 

  25. Kale L, Skeel R, Bhandarkar M, Brunner R, Gursoy A, Krawetz N, Phillips J, Shinozaki A, Varadarajan K, Schulten K (1999) J Comput Phys 151:283

    Article  CAS  Google Scholar 

  26. MacKerell AD Jr, Bashford D, Bellott M, Dunbrack RL Jr, Evanseck J, Field M, Fischer JS, Gao J, Guo H, Ha S, Joseph D, Kuchnir L, Kuczera K, Lau FTK, Mattos C, Michnick S, Ngo T, Nguyen DT, Prodhom B, Roux B, Schlenkrich M, Smith J, Stote R, Straub J, Watanabe M, Wiorkiewicz-Kuczera J, Yin D, Karplus M (1992) FASEB J 6:A143–A143

    Google Scholar 

  27. MacKerell AD Jr, Bashford D, Bellott M, Dunbrack RL Jr, Evanseck J, Field M, Fischer JS, Gao J, Guo H, Ha S, Joseph D, Kuchnir L, Kuczera K, Lau FTK, Mattos C, Michnick S, Ngo T, Nguyen DT, Prodhom B, Reiher IWE, Roux B, Schlenkrich M, Smith J, Stote R, Straub J, Watanabe M, Wiorkiewicz-Kuczera J, Yin D, Karplus M (1998a) J Phys Chem B 102:3586–3616

    Article  CAS  Google Scholar 

  28. Schlenkrich M, Brickmann J, MacKerell AD Jr, Karplus M (1996) A molecular perspective from computation and experiment. In: Merz KM, Roux B (eds) Birkhauser, Boston MA, pp 31–81

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

    Article  CAS  Google Scholar 

  30. Grubmuller H, Heller H, Windemuth A, Schulten K (1991) Mol Sim 6:121–142

    Article  Google Scholar 

  31. Schlick T, Skeel R, Brunger A, Kale L, Board JA Jr, Hermans J, Schulten K (1999) Algorithmic challenges in computational molecular biophysics. J Comput Phys 151:9–48

    Article  CAS  Google Scholar 

  32. Brunger (1992) X-PLOR, Version 3.1: Yale University New Haven CT

  33. MacKerell AD Jr, Brooks B, Brooks CL III, Nilsson L, Roux B, Won Y, Karplus M (1998b) In: Schleyer P (ed) The encyclopedia of computational chemistry. John Wiley & Sons, Chichester, UK, pp 271–277

  34. Ryckaert J-P, Ciccotti G, Berendsen HJC (1977) J Comput Phys 23:327–341

    Article  CAS  Google Scholar 

  35. Essmann U, Perera L, Berkowitz ML, Darden T, Lee H, Pedersen LG (1995) J Chem Phys 103:8577

    Article  CAS  Google Scholar 

  36. Laskoswki RA, MacArthur MW, Moss DS, Thorton JM (1993) J Appl Cryst 26:283–291

    Article  Google Scholar 

  37. Colovos K, Yeates TO (1993) Protein Sci 2:1511–1519

    Article  CAS  Google Scholar 

  38. Vriend G (1990) J Mol Graph 8:52–56

    Article  CAS  Google Scholar 

  39. Hooft RWW, Vriend G, Sander C, Abola EE (1996) Nature 381:272

    Article  CAS  Google Scholar 

  40. Guex N, Peitsch MC (1997) Electrophoresis 18:2714–2723

    Article  CAS  Google Scholar 

  41. Dundas J, Ouyang Z, Tseng J, Binkowski A, Turpaz Y, Liang J (2006) Nucleic Acids Res 34:W116–W118

    Google Scholar 

  42. Schulz-Gasch T, Stahl M (2003) J Mol Model 9:47–57

    CAS  Google Scholar 

  43. Rossmann MG, Moras D, Olsen KW (1974) Nature 250:194–199

    Article  CAS  Google Scholar 

  44. Zhong RW, Morrison H III, Himmelsbach DS, Poole FL II, Ye ZH (2000) Plant Physiol 124:563–577

  45. Hoffmann L, Maury S, Bergdoll M, Thion L, Erard M, Legrand M (2001) J Biol Chem 276:36831–36838

    Article  CAS  Google Scholar 

Download references

Acknowledgements

The authors are thankful to the CSIR, New Delhi, for financial assistance in the form of a research project (CSIR-NMITLI) on paper and pulp.

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Authors and Affiliations

  1. Department of Genetics, Osmania University, Hyderabad, 500 007, India

    Nataraj Sekhar Pagadala, P. S. Reddy, Ranadheer Kumar, V. L. Sirisha, S. Prashant & P. B. Kavi Kishor

  2. Plant Tissue Culture Division, National Chemical Laboratory, Pune, 411 008, India

    Manish Arha, Bashir Khan & S. K. Rawal

  3. Department of Botany, Osmania University, Hyderabad, 500 007, India

    K. Janardhan Reddy

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  1. Nataraj Sekhar Pagadala
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  2. Manish Arha
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Correspondence to P. B. Kavi Kishor.

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Sekhar Pagadala, N., Arha, M., Reddy, P.S. et al. Phylogenetic analysis, homology modelling, molecular dynamics and docking studies of caffeoyl–CoA-O- methyl transferase (CCoAOMT 1 and 2) isoforms isolated from subabul (Leucaena leucocephala). J Mol Model 15, 203–221 (2009). https://doi.org/10.1007/s00894-008-0395-8

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  • DOI: https://doi.org/10.1007/s00894-008-0395-8

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