Flavonoids play beneficial roles in various human diseases. In this study, a flavonoid library was employed to probe inhibitors of d-glycero-β-d-manno-heptose-1-phosphate adenylyltransferase from Burkholderia pseudomallei (BpHldC) and two flavonoids, epigallocatechin gallate (EGCG) and myricetin, have been discovered. BpHldC is one of the essential enzymes in the ADP-l-glycero-β-d-manno-heptose biosynthesis pathway constructing lipopolysaccharide of B. pseudomallei. Enzyme kinetics study showed that two flavonoids work through different mechanisms to block the catalytic activity of BpHldC. Among them, a docking study of EGCG was performed and the binding mode could explain its competitive inhibitory mode for both ATP and βG1P. Analyses with EGCG homologs could reveal the important functional moieties, too. This study is the first example of uncovering the inhibitory activity of flavonoids against the ADP-l-glycero-β-d-manno-heptose biosynthesis pathway and especially targeting HldC. Since there are no therapeutic agents and vaccines available against melioidosis, EGCG and myricetin can be used as templates to develop antibiotics over B. pseudomallei.
-
Cover Image
Cover Image
Tumor organoids are a relevant, 3-dimensional, culture method which allows long-term growth preserving the stem cell identity and reconstituting to some extent the morphological and phenotypic heterogeneity of the original tumor. Representative fluorescence image of a tumour organoid derived from patient derived GSCs after 23 days of culture, stained for anti-αTubulin (microtubules, white) and Phalloidin (actin red). In this issue Pinto and colleagues (pp. 21–39) observed that different types of cell protrusions (TMs and TNTs) connecting cells were present and coexist inside the organoid. The image was captured by Inés Saenz-de-Santa-Maria with an inverted confocal microscope LSM700, Pln-Apo 10X/0.45 objective.
Inhibition of d-glycero-β-d-manno-heptose 1-phosphate adenylyltransferase from Burkholderia pseudomallei by epigallocatechin gallate and myricetin
Suwon Kim, Seri Jo, Mi-Sun Kim, Heejin Kam, Dong Hae Shin; Inhibition of d-glycero-β-d-manno-heptose 1-phosphate adenylyltransferase from Burkholderia pseudomallei by epigallocatechin gallate and myricetin. Biochem J 15 January 2021; 478 (1): 235–245. doi: https://doi.org/10.1042/BCJ20200677
Download citation file:
Sign in
Sign in to your personal account
Captcha Validation Error. Please try again.