SALMON: solvent accessibility, ligand binding, and mapping of ligand orientation by NMR spectroscopy.

Journal article

Quinone oxidoreductase 2 (NQO2) binds the prodrug tretazicar (also known as CB1954, 5-(aziridin-1-yl)-2,4-dinitrobenzamide), which exhibits a profound antitumor effect in human cancers when administered together with caricotamide. X-ray structure determination allowed for two possible orientations of the ligand. Here we describe a new NMR method, SALMON (solvent accessibility, ligand binding, and mapping of ligand orientation by NMR spectroscopy), based on waterLOGSY to determine the orientation of a ligand bound to a protein by mapping its solvent accessibility, which was used to unambiguously determine the orientation of CB1954 in NQO2.

Authors: Ludwig, C; Michiels, P; Wu, X; Kavanagh, K; Pilka, E

• Publication status: Published
• Journal: Journal of medicinal chemistry
• Volume: 51
• Issue: 1
• Pages: 1-3
• Publication date: 2008-01-01
• DOI: 10.1021/jm701020f
• EISSN: 1520-4804
• ISSN: 0022-2623
• Language: English
• Keywords: NAD(P)H Dehydrogenase (Quinone); Protein Binding; Models, Molecular; Solvents; Binding Sites; Aziridines; Prodrugs; Antineoplastic Agents; Ligands; Water; Magnetic Resonance Spectroscopy