5 years ago

A New Potent Inhibitor of Glycogen Phosphorylase Reveals the Basicity of the Catalytic Site

A New Potent Inhibitor of Glycogen Phosphorylase Reveals the Basicity of the Catalytic Site
Thanasis Gimisis, Alessandro Venturini, Michael Mamais, Filippo Monti, Thomas Gustavsson, Virginia Kouloumoundra, Dimitra Markovitsi, Alessandra Degli Esposti, Evangelia D. Chrysina
The design and synthesis of a glucose-based acridone derivative (GLAC), a potent inhibitor of glycogen phosphorylase (GP) are described. GLAC is the first inhibitor of glycogen phosphorylase, the electronic absorption properties of which are clearly distinguishable from those of the enzyme. This allows probing subtle interactions in the catalytic site. The GLAC absorption spectra, associated with X-ray crystallography and quantum chemistry calculations, reveal that part of the catalytic site of GP behaves as a highly basic environment in which GLAC exists as a bis-anion. This is explained by water-bridged hydrogen-bonding interactions with specific catalytic site residues. It's so basic: Glycogen phosphorylase (GP) is an enzyme that plays a key role in glucose regulation. The design and synthesis of a new potent inhibitor of GP is described. Exploiting its optical properties, it is shown that, due to an extended hydrogen-bonding network, the local pH in the GP catalytic site is higher than 12.

Publisher URL: http://onlinelibrary.wiley.com/resolve/doi

DOI: 10.1002/chem.201701591

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.