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Vol.4 , No. 5, Publication Date: Oct. 13, 2017, Page: 74-81
 reductase was reported. In the current study, the precise interaction as well as the binding capacity of morelloflavone and its naturally occurring derivatives were determined with the aid of <i>in silico</i> experimental approach and compared with known statin as control. The results obtained showed that morelloflavone displayed the best binding capacity among the compounds and occupied HMG-binding pocket on HMG-COA reductase thereby blocking access of substrates to the enzyme active site. The molecular analysis clearly revealed that morelloflavone has the highest affinity to the enzyme compared with its derivatives but lower affinity than the control ligand, atorvastatin. The luteolin subunit of morelloflavone was found buried within the shallow hydrophobic pocket where hydrogen bond interactions were seen with residues Asn755, Glu665, Ser684, Cys561, Asp690 and Ala856. The binding pose and precise interaction of morelloflavone with the enzyme was comparable to that of statin. Considering the bulky hydrophobic structure of the biflavonoids, the contribution of van der waals interactions to the binding strength observed between HMG-COA reductase and morelloflavone is predictable. The binding affinity of morelloflavone, as seen clearly in this work, is in agreement with previous reports obtained from <i>in vitro</i> experiments. Hence, this work provides insight on the direct interaction and inhibitory potential of these plant-derived biflavonoids on HMG-COA reductase as an anti-hypercholesterolemia target.&picture=http://www.aascit.org/aascit/decorators/img/journal/903.jpg)
| [1] | Ogunwa Tomisin Happy, Centre for Bio-computing and Drug Development, Adekunle Ajasin University, Akungba-Akoko, Nigeria; Department of Biochemistry, Adekunle Ajasin University, Akungba-Akoko, Nigeria. |
| [2] | Ayenitaju Folasade Catherine, Department of Biochemistry, University of Ibadan, Ibadan, Nigeria. |
Morelloflavone and its derivatives are plant-derived biflavonoids with diverse pharmacological activities including anti-hypercholesterolemia. As natural compounds, researches are still aimed at elucidating possible mechanism of their known biological activities. These compounds may serve as sources of cheap pharmaceutical agents with less or no toxic effects. Previously, using in vitro analysis, the inhibitory effect of morelloflavone on 3-hydroxy-3-methylglutaryl-CoA (HMG-COA) reductase was reported. In the current study, the precise interaction as well as the binding capacity of morelloflavone and its naturally occurring derivatives were determined with the aid of in silico experimental approach and compared with known statin as control. The results obtained showed that morelloflavone displayed the best binding capacity among the compounds and occupied HMG-binding pocket on HMG-COA reductase thereby blocking access of substrates to the enzyme active site. The molecular analysis clearly revealed that morelloflavone has the highest affinity to the enzyme compared with its derivatives but lower affinity than the control ligand, atorvastatin. The luteolin subunit of morelloflavone was found buried within the shallow hydrophobic pocket where hydrogen bond interactions were seen with residues Asn755, Glu665, Ser684, Cys561, Asp690 and Ala856. The binding pose and precise interaction of morelloflavone with the enzyme was comparable to that of statin. Considering the bulky hydrophobic structure of the biflavonoids, the contribution of van der waals interactions to the binding strength observed between HMG-COA reductase and morelloflavone is predictable. The binding affinity of morelloflavone, as seen clearly in this work, is in agreement with previous reports obtained from in vitro experiments. Hence, this work provides insight on the direct interaction and inhibitory potential of these plant-derived biflavonoids on HMG-COA reductase as an anti-hypercholesterolemia target.
Keywords
Morelloflavone, HMG-COA Reductase, Hypercholesterolemia, Molecular Interaction
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