Marmesin and Marmelosin Interact with the Heparan Sulfatase-2 Active Site: Potential Mechanism for Phytochemicals from Bael Fruit Extract as Antitumor Therapeutics

Human heparan sulfatase-2 (HSULF-2) is an oncoprotein overexpressed in the surface of all types of tumor cells and its activity plays a critical role in cancer survival and progression. Our previous studies have shown that bael fruit extract, containing marmesin and marmelosin, inhibits the HSULF-2...

Full description

Saved in:
Bibliographic Details
Published in:Oxidative medicine and cellular longevity 2023, Vol.2023, p.9982194-19
Main Authors: Hemakumar, C., Ravindranath, B. S., Ravishankar, G. A., Ramirez, D. C., Kiran, S. V.
Format: Article
Language:English
Subjects:
Binding sites
Breast cancer
Catalytic Domain
Cell cycle
Disease
Drugs
Fruit
Functional foods & nutraceuticals
Genes
Glycosaminoglycans
Heparan sulfate
Humans
Ligands
Molecular Docking Simulation
Pharmacokinetics
Phytochemicals
Phytochemicals - pharmacology
Plant Extracts - pharmacology
Proteins
Sulfatases
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Human heparan sulfatase-2 (HSULF-2) is an oncoprotein overexpressed in the surface of all types of tumor cells and its activity plays a critical role in cancer survival and progression. Our previous studies have shown that bael fruit extract, containing marmesin and marmelosin, inhibits the HSULF-2 activity and kills breast tumor cells, but the mechanism of these processes remains fairly known mainly because the HSULF-2’s 3D structure is partially known. Herein, we aimed at providing an in silico molecular mechanism of the inhibition of human HSULF-2 by phytochemicals from bael fruit extract. Pharmacokinetic parameters of the main phytochemicals contained in the bael fruit extract, sequence-based 3D structure of human HSULF-2, and the interaction of bael fruit’s phytochemicals with the enzyme active site was modeled, evaluated, and verified. Docking studies revealed marmesin and marmelosin as potential inhibitors with binding score -8.5 and -7.7 Kcal/mol; these results were validated using molecular dynamics simulations, which exhibited higher stability of the protein-ligand complexes. Taking together, with our earlier in vitro data, our computational analyses suggest that marmesin and marmelosin interact at the active site of HSULF-2 providing a potential mechanism for its inhibition and consequent antitumor activity by phytochemicals contained in the bael fruit extract.
ISSN:1942-0900
1942-0994
DOI:10.1155/2023/9982194