Journal of Molecular Modeling

, 15:203 | Cite as

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)

  • Nataraj Sekhar Pagadala
  • Manish Arha
  • P. S. Reddy
  • Ranadheer Kumar
  • V. L. Sirisha
  • S. Prashant
  • K. Janardhan Reddy
  • Bashir Khan
  • S. K. Rawal
  • P. B. Kavi KishorEmail author
Original Paper


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.


Caffeoyl–CoA 3-O-methyl transferase Docking Modelling S-adenosyl homocysteine 



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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Copyright information

© Springer-Verlag 2008

Authors and Affiliations

  • Nataraj Sekhar Pagadala
    • 1
  • Manish Arha
    • 2
  • P. S. Reddy
    • 1
  • Ranadheer Kumar
    • 1
  • V. L. Sirisha
    • 1
  • S. Prashant
    • 1
  • K. Janardhan Reddy
    • 3
  • Bashir Khan
    • 2
  • S. K. Rawal
    • 2
  • P. B. Kavi Kishor
    • 1
    Email author
  1. 1.Department of GeneticsOsmania UniversityHyderabadIndia
  2. 2.Plant Tissue Culture DivisionNational Chemical LaboratoryPuneIndia
  3. 3.Department of BotanyOsmania UniversityHyderabadIndia

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