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.
CR UK Institute for Cancer Studies, University of Birmingham, Vincent Drive, Edgbaston, Birmingham B15 2TT, UK.
Christian
C
Ludwig
Paul J A
PJ
Michiels
Xiaoqiu
X
Wu
Kathryn L
KL
Kavanagh
Ewa
E
Pilka
Anna
A
Jansson
Udo
U
Oppermann
Ulrich L
UL
Günther
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