5 years ago

In Silico and in Vitro Interactions between Short Chain Fatty Acids and Human Histone Deacetylases

In Silico and in Vitro Interactions between Short Chain Fatty Acids and Human Histone Deacetylases
Dorinda Yan Qin Kioh, Rou Hui Ho, James Chun Yip Chan, Eric Chun Yong Chan, Bee Wah Lee, Hao Fan
Short chain fatty acids (SCFAs) are postulated to modulate the immune development of neonates via epigenetic regulations such as histone deacetylase (HDAC) inhibition. In the context of atopic diseases, the inhibition of HDAC maintains T-cell homeostasis and induces naïve T-cell differentiation into adaptive Treg, which regulates the production of anti-inflammatory cytokines and suppression of Th2 immune responses. We investigated the structure–inhibition relationships of SCFAs with class I HDAC3 and class IIa HDAC7 using in silico docking simulation and the in vitro human recombinant HDAC inhibition assay. In silico docking simulation demonstrated that the lower binding energy of SCFAs toward HDACs was associated with the longer aliphatic chain length of SCFAs. Conversely, branching of SCFAs increased their binding energies toward both HDAC3 and HDAC7. The in vitro HDAC inhibition assay revealed that SCFAs more potently inhibit HDAC3 than HDAC7, with butyric acid being the most potent HDAC3 inhibitor among SCFAs (IC50 = 0.318 mM). In conclusion, our findings inform novel structural relationships between SCFAs and HDAC3 versus HDAC7. Future investigation of human disposition of SCFAs is important to establish their effects on innate versus adaptive immunity.

Publisher URL: http://dx.doi.org/10.1021/acs.biochem.7b00508

DOI: 10.1021/acs.biochem.7b00508

You might also like
Discover & Discuss Important Research

Keeping up-to-date with research can feel impossible, with papers being published faster than you'll ever be able to read them. That's where Researcher comes in: we're simplifying discovery and making important discussions happen. With over 19,000 sources, including peer-reviewed journals, preprints, blogs, universities, podcasts and Live events across 10 research areas, you'll never miss what's important to you. It's like social media, but better. Oh, and we should mention - it's free.

  • Download from Google Play
  • Download from App Store
  • Download from AppInChina

Researcher displays publicly available abstracts and doesn’t host any full article content. If the content is open access, we will direct clicks from the abstracts to the publisher website and display the PDF copy on our platform. Clicks to view the full text will be directed to the publisher website, where only users with subscriptions or access through their institution are able to view the full article.