New Small‐Molecule Binding Site

  • Author: Ruben Ragg
  • Published Date: 06 May 2018
  • Source / Publisher: ChemBioChem/Wiley-VCH
  • Copyright: Wiley-VCH Verlag GmbH & Co. KGaA
thumbnail image: New Small‐Molecule Binding Site

Related Societies

Protein–protein interactions (PPs) are central to most biological processes and are, therefore, attractive therapeutic targets. The targeting of those interactions, however, remains a challenge. Protein-Observed Fluorine NMR (PrOF NMR) spectroscopy is an emerging technique for screening and characterizing small molecule-protein interactions. The choice of which amino acid to label for PrOF NMR can be critical for analysis.

William C. K. Pomerantz, University of Minnesota, Minneapolis, USA, and colleagues have reported the first use of a protein containing two different fluoroaromatic amino acids for NMR studies. The team used the KIX domain of the CREB Binding Protein (CBP/p300) as a model system. They examined KIX binding interactions with previously reported and novel small molecules and identified a new binding site distinct from those used by native transcription factors. Such a new binding site provides an opportunity to regulate KIX PPIs allosterically, either positively or negatively.

According to the authors, metabolic labeling with multiple fluorinated amino acids provides useful probes for further studying ligand binding.


Article Views: 1762

Sign in Area

Please sign in below

Additional Sign In options

Please note that to comment on an article you must be registered and logged in.
Registration is for free, you may already be registered to receive, e.g., the newsletter. When you register on this website, please ensure you view our terms and conditions. All comments are subject to moderation.

Article Comments - To add a comment please sign in

If you would like to reuse any content, in print or online, from, please contact us first for permission. more

Follow on Facebook Follow on Twitter Follow on YouTube Follow on LinkedIn Follow on Instagram RSS Sign up for newsletters

Magazine of Chemistry Europe (16 European Chemical Societies) published by Wiley-VCH