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Structural Basis for the High-Affinity Inhibition of Mammalian Membranous Adenylyl Cyclase by 2`,3`-O-(N-Methylanthraniloyl)-Inosine 5`-Triphosphate

Hübner, Melanie ; Dixit, A. ; Mou, T.-C. ; Lushington, Gerald H. ; Pinto, Cibele S. ; Gille, A. ; Geduhn, Jens ; König, Burkhard ; Sprang, S. R. ; Seifert, Roland



Abstract

2',3'-O-(N-Methylanthraniloyl)-inosine 5'-triphosphate (MANT-ITP) is the most potent inhibitor of mammalian membranous adenylyl cyclase (mAC) 5 (AC5, Ki, 1 nM) yet discovered and surpasses the potency of 2',3'-O-(N-methylanthraniloyl)-guanosine 5'-triphosphate (MANT-GTP) 55-fold (Göttle et al., J Pharmacol Exp Ther 329:1156-1165 (2009)). AC5 inhibitors may be valuable drugs for treatment of heart ...

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