Title:In Silico Docking of Vitamin E Isomers on Transport Proteins
VOLUME: 16 ISSUE: 4
Author(s):Nurul Syeefa Zulkiflee, Siti Amilia Awang, Woo Xian Ming, Muhammad Fauzan Wira’i Kamilan, M Yuveneshwari Mariappan and Tan Jen Kit*
Affiliation:Department of Biochemistry, Faculty of Medicine, Universiti Kebangsaan Malaysia, 56000 Cheras, Department of Biochemistry, Faculty of Medicine, Universiti Kebangsaan Malaysia, 56000 Cheras, Department of Biochemistry, Faculty of Medicine, Universiti Kebangsaan Malaysia, 56000 Cheras, Department of Biochemistry, Faculty of Medicine, Universiti Kebangsaan Malaysia, 56000 Cheras, Department of Biochemistry, Faculty of Medicine, Universiti Kebangsaan Malaysia, 56000 Cheras, Department of Biochemistry, Faculty of Medicine, Universiti Kebangsaan Malaysia, 56000 Cheras
Keywords:Tocopherols, tocotrienols, carrier proteins, molecular docking simulation, αTTP, GLTP.
Abstract:
Background: Vitamin E is comprised of α, β, γ and δ-tocopherols (Ts) and α, β, γ and δ-
tocotrienols (T3s). Vitamin E has neuroprotective antioxidant, anti-cancer, and cholesterol-lowering
effects. Intracellular trafficking of these isomers remains largely unknown, except for αT which is
selectively transported by αT transfer protein (αTTP).
Objective: This study aimed to determine the binding of vitamin E isomers on transport proteins
using in silico docking.
Methods: Transport proteins were selected using AmiGo Gene Ontology tool based on the same
molecular function annotation as αTTP. Protein structures were obtained from the Protein Data
Bank. Ligands structures were obtained from ZINC database. In silico docking was performed
using SwissDock.
Results and Discussion: A total of 6 transport proteins were found: SEC14-like protein 2,
glycolipid transfer protein (GLTP), pleckstrin homology domain-containing family A member 8,
collagen type IV alpha-3-binding protein, ceramide-1-phosphate transfer protein and afamin.
Compared with other transport proteins, αTTP had the highest affinities for all isomers except βT3.
Binding order of vitamin E isomers toward αTTP was γT > βT > αT > δT > αT3 > γT3 > δT3 > βT3.
GLTP had a higher affinity for tocotrienols than tocopherols. βT3 bound stronger to GLTP than αTTP.
Conclusion: αTTP remained as the most preferred transport protein for most of the isomers. The
binding affinity of αT toward αTTP was not the highest than other isomers suggested that other
intracellular trafficking mechanisms of these isomers may exist. GLTP may mediate the intracellular
transport of tocotrienols, especially βT3. Improving the bioavailability of these isomers may enhance
their beneficial effects to human.
