NOVEL ACTIVE SITE INHIBITION OF O-LINKED N-ACETYL GLUCOSAMINE TRANSFERASE (OGT) FROM ALKALOID LIBRARY

Main Article Content

FLORENCE WUMI AKINYEMI
OLANREWAJU ADIRU AMEEN
TAJUDEEN O. OSENI
ABDULHAMEED OLUWATOMI ALLI
BASHIR DAYO ABDULRAHMAN
ABDULHAKEEM FUNSHO AHMED

Abstract

O-linked-N- acetyl glucosaminetransferase (OGT) is an important enzyme which regulates many important cellular processes through posttranscriptional modification of the nuclear and cytosolic proteins. OGT catalyzes the attachment of N- acetylglucosamine portion of uridine diphosphate N- acetyl glucosamine (UDP- GlcNac) to the serine and threonine residues of nuclear and cytoplasmic proteins of multicellular eukaryote in protein O-GlcNacylation process. Hyperglycemia increases GlcNacylation of proteins. GlcNacylation has been linked to some human diseases, such as cardiovascular diseases, diabetes mellitus, neurodegenerative diseases, and cancer. Several inhibitors of the enzyme have been explored in the treatment of the diseases associated with it. In this study, alkaloids were mined from online database and screened computationally using molecular docking approach. 290 alkaloids were retrieved and docked against OGT, using OGT complexed with a thio – linked substrate as the control, and the docking approach predicted 14-norpseurotinA (14-NSA), Protoveratrine B (PB) and 3-(4-methoxyphenyl)-3-[[2-(4-methoxyphenyl)-1-oxoethyl] amino] propanoic acid (MPOAPA) to be suitable inhibitors of OGT, through their interaction and binding pose with the amino acid residues at the substrate-binding site of the protein, with a  docking score of -11.106, -9.176 and -8.269 respectively. Additionally, the hit compounds were then subjected to ADMETox screening to predict their drug – likeness.  The ADMETox analysis  predicted that 14-NSA, and MPOAPA shows more drug-like characteristics compared to PB and the co crystallised ligand by obeying the rule of five for drug development. However, natural bioactive compounds 14-NSA, and MPOAPA could be a potential active site inhibitor of OGT in the treatment of cancer, diabetes, neurodegenerative diseases and cardiovascular diseases caused by aberrant O- GlcNacylation.

Keywords:
O-Linked-N- acetyl glucosaminetransferase (OGT), uridine diphosphate N- acetyl glucosamine (UDP- GlcNac), molecular docking; alkaloids; O-GlcNacylation

Article Details

How to Cite
AKINYEMI, F. W., AMEEN, O. A., OSENI, T. O., ALLI, A. O., ABDULRAHMAN, B. D., & AHMED, A. F. (2022). NOVEL ACTIVE SITE INHIBITION OF O-LINKED N-ACETYL GLUCOSAMINE TRANSFERASE (OGT) FROM ALKALOID LIBRARY. Journal of Biochemistry International, 9(4), 94-103. https://doi.org/10.56557/jobi/2022/v9i47991
Section
Original Research Article

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