NMR-Based Determination of the 3D Structure of the Ligand–Protein Interaction Site without Protein Resonance Assignment

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• 作者：Julien Orts ; Marielle Aulikki Wälti ; May Marsh ; Laura Vera ; Alvar D. Gossert ; Peter Güntert ; Roland Riek
• 刊名：Journal of the American Chemical Society
• 出版年：2016
• 出版时间：April 6, 2016
• 年：2016
• 卷：138
• 期：13
• 页码：4393-4400
• 全文大小：570K
• ISSN：1520-5126

文摘

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.