In silico approach of azadirachtin binding with actins.

Abstract:

:In silico docking analysis reported here suggests that insect cellular cytoskeletal beta-actin could be the target of Azadirachtin A (Aza-the principle bioactive compound of neem seeds). The best docking energy of -40.09 kcal/mol at 8.73 A RMSD and predicted hydrogen bond between Arg210 and carboxymethyl group of Aza accompanied with seven hydrophobic interactions in the proposed binding site strongly support this hypothesis. This is of specific interest due to the non-affinity of Aza to mammalian beta-actins under the same set of conditions, although beta-actins across the species are highly conserved. Our results show that few scattered amino acid changes have caused significant steric hindrance in the binding pocket for mammalian beta-actin, causing a reverse orientation of Aza. These results suggest a model to support the recently observed biological effects caused by Aza in Drosophila cytoskeletal elements and explain why Aza is highly specific to insects than mammals.

authors

Pravin Kumar R,Manoj MN,Kush A,Annadurai RS

doi

10.1016/j.ibmb.2007.03.010

subject

Has Abstract

pub_date

2007-06-01 00:00:00

pages

635-40

issue

6

eissn

0965-1748

issn

1879-0240

pii

S0965-1748(07)00063-X

journal_volume

37

pub_type

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