Metal coordination-based inhibitors of adenylyl cyclase: novel potent P-site antagonists

…, M Bao, DB Cherbavaz, JE Tomlinson…

Index: Levy, Daniel E.; Bao, Ming; Cherbavaz James, Diana B.; Tomlinson; Sedlock, David M.; Homcy, Charles J.; Scarborough, Robert M. Journal of Medicinal Chemistry, 2003 , vol. 46, # 11 p. 2177 - 2186

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Citation Number: 22

Abstract

The adenylyl cyclases (ACs) are a family of intracellular enzymes associated with signal transduction by virtue of their ability to convert ATP to cAMP. The catalytic mechanism of this transformation proceeds through initial binding of ATP to the so-called purine binding site (P- site) of the enzyme followed by metal-mediated cyclization with loss of pyrophosphate. Crystallographic analysis of ACs with known inhibitors reveals the presence of two metals ...