NMR-Based Determination of the 3D Structure of the Ligand-Protein Interaction Site without Protein Resonance Assignment
- Author(s)
- Julien Orts, Marielle Aulikki Wälti, May Marsh, Laura Vera, Alvar D. Gossert, Peter Güntert, Roland Riek
- Abstract
Molecular replacement in X-ray crystallography is the prime method for establishing structure–activity relationships of pharmaceutically relevant molecules. Such an approach is not available for NMR. Here, we establish a comparable method, called NMR molecular replacement (NMR2). The method requires experimentally measured ligand intramolecular NOEs and ligand–protein intermolecular NOEs as well as a previously known receptor structure or model. Our findings demonstrate that NMR2 may open a new avenue for the fast and robust determination of the interaction site of ligand–protein complexes at atomic resolution.
- Organisation(s)
- External organisation(s)
- Eidgenössische Technische Hochschule Zürich, Paul Scherrer Institute, Novartis Pharma AG, Johann Wolfgang Goethe-Universität Frankfurt am Main, Frankfurt Institute for Advanced Studies (FIAS)
- Journal
- Journal of the American Chemical Society
- Volume
- 138
- Pages
- 4393-4400
- No. of pages
- 8
- ISSN
- 0002-7863
- DOI
- https://doi.org/10.1021/jacs.5b12391
- Publication date
- 04-2016
- Peer reviewed
- Yes
- Austrian Fields of Science 2012
- 106006 Biophysics, 106002 Biochemistry
- Keywords
- ASJC Scopus subject areas
- General Chemistry, Biochemistry, Catalysis, Colloid and Surface Chemistry
- Portal url
- https://ucrisportal.univie.ac.at/en/publications/1f459d4b-b1b0-4ad3-a15b-87dc76f3bc78