Hydroxamate based inhibitors of adenylyl cyclase. Part 1: the effect of acyclic linkers on P-site binding

DE Levy, C Marlowe, K Kane-Maguire, M Bao…

Index: Levy, Daniel E; Marlowe, Charles; Kane-Maguire, Kim; Bao, Ming; Cherbavaz, Diana B.; Tomlinson, James E.; Sedlock, David M.; Scarborough, Robert M. Bioorganic and Medicinal Chemistry Letters, 2002 , vol. 12, # 21 p. 3085 - 3088

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Citation Number: 11

Abstract

The adenylyl cyclases (ACs) are a family of enzymes that are key elements of 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 purine binding site (P-site) followed by metal mediated cyclization with loss of pyrophosphate. Crystallographic analysis of ACs with known inhibitors reveals the presence of two metals in the active site. ...

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