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OJBTM
Online Journal of Bioinformatics ©
Volume
11 (1):103-124, 2009
Phylogenetic analysis, homology modeling,
molecular dynamics, docking and structure based designing of new inhibitors against
cinnamyl alcohol dehydrogenase
(CAD) cloned and sequenced from a leguminous tree subabul
(Leucaena leucocephala)
Sekhar NP1, Kumar RD2,
Sirisha VL2, Prashant
S2, Kavi Kishor
PB1
Department of Genetics,
Sekhar NP, Kumar RD, Sirisha
VL, Prashant S, Kavi Kishor PB, Phylogenetic analysis,
homology modeling, molecular dynamics, docking and structure based designing of
new inhibitors against cinnamyl alcohol dehydrogenase (CAD) cloned and sequenced from a leguminous
tree subabul (Leucaena leucocephala), Online J Bioinformatics, 11 (1):103-124,
2009. Cinnamyl-alcohol dehydrogenase
(CAD; EC 1.1.1.195) catalyzes the final step in the branch of phenylpropanoid synthesis specific for production of lignin
monomers. The homology model of CAD enzyme cloned and sequenced by us from subhabul was build by energy minimization and molecular
dynamics in a solvated water layer. The refined protein showed that the enzyme
have 11 a-helices and 20 β-sheets with a catalytic and nucleotide binding
domains forming a rossmanfold. Superimposition of the
refined model with the template showed 1.38Å. Structural analysis of CAD with
the templates revealed highly conserved GHE pattern. Docking studies show that
NADPH acts a cofactor for the enzyme CAD from subhabul.
In the presence of co-factor, 5-hydroxy coniferyl aldehyde binds with high affinity with the enzyme
predicting to be the major substrate for the enzyme CAD. Pharmacophore
based docking of 5-hydroxy coniferyl aldehyde show that 5-(2-hydroxyethyl)-6-methyl-pyrimidine-2, 4-diol inhibitor binds with high affinity compared to the
natural substrates. Docking studies also shows that His48, Ser49 and His52 plays an important role in binding of the substrates,
products and inhibitors.
Keywords: Cinamyl
alcohol dehydrogenase, homology modeling, docking