SALMON: solvent accessibility, ligand binding, and mapping of ligand orientation by NMR spectroscopy.
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.
Ludwig
Christian
C
CR UK Institute for Cancer Studies, University of Birmingham, Vincent Drive, Edgbaston, Birmingham B15 2TT, UK.
Michiels
Paul J A
PJ
Wu
Xiaoqiu
X
Kavanagh
Kathryn L
KL
Pilka
Ewa
E
Jansson
Anna
A
Oppermann
Udo
U
Günther
Ulrich L
UL
D000970:Antineoplastic Agents / Q000737:chemistry*; D001388:Aziridines / Q000737:chemistry*; D001665:Binding Sites; D008024:Ligands; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000737:chemistry*; D011355:Prodrugs / Q000737:chemistry*; D011485:Protein Binding; D012997:Solvents; D014867:Water / Q000737:chemistry*
D000970:Antineoplastic Agents; D001388:Aziridines; D008024:Ligands; D011355:Prodrugs; D012997:Solvents; D014867:Water; C100099:tretazicar; D016660:NAD(P)H Dehydrogenase (Quinone); C447479:NQO1 protein, human