Abstract
An extract of bark from the tropical rainforest plant Byrsonima crassifolia was screened for inhibition of diubiquitin formation by the human ubiquitin-conjugating enzyme E2-25K. Activity assays with both the full-length enzyme and a truncated, active catalytic UBC domain revealed that the extract contained inhibitory properties. Separation of the extract into individual components and additional screens identified vitexin as the active inhibitor. An IC50 for vitexin was calculated to be approximately 0.5 mM. Molecular modeling simulations were used to predict the mode of inhibition and NMR spectra were used to confirm the binding site of vitexin to E2-25K.
Publication types
-
Research Support, N.I.H., Extramural
-
Research Support, Non-U.S. Gov't
-
Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
-
Apigenin / chemistry
-
Apigenin / pharmacology*
-
Binding Sites
-
Biological Products
-
Gene Expression Regulation / drug effects*
-
Humans
-
Malpighiaceae / chemistry*
-
Models, Molecular
-
Plant Bark / chemistry
-
Plant Extracts / chemistry
-
Plant Extracts / pharmacology
-
Plants / chemistry
-
Protein Binding
-
Protein Conformation
-
Ubiquitin-Conjugating Enzymes / antagonists & inhibitors*
-
Ubiquitin-Conjugating Enzymes / metabolism
-
Ubiquitins / genetics
-
Ubiquitins / metabolism*
Substances
-
Biological Products
-
Plant Extracts
-
UBD protein, human
-
Ubiquitins
-
Apigenin
-
vitexin
-
UBE2K protein, human
-
Ubiquitin-Conjugating Enzymes