Inhibitors of membranous adenylyl cyclases

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Pro-nucleotide inhibitors of adenylyl cyclases in intact cells.

9-substituted adenine derivatives with protected phosphoryl groups were synthesized and tested as inhibitors of adenylyl cyclase in isolated enzyme and intact cell systems. Protected 3'-phosphoryl derivatives of 2',5'-dideoxyadenosine (2',5'-dd-Ado) and beta-l-2',5'-dd-Ado, protected 5'-phosphoryl derivatives of beta-l-2',3'-dd-Ado, and protected phosphoryl derivatives of two 9-(2-phosphonometh...

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Regulation of prokaryotic adenylyl cyclases by CO2.

The Slr1991 adenylyl cyclase of the model prokaroyte Synechocystis PCC 6803 was stimulated 2-fold at 20 mM total C(i) (inorganic carbon) at pH 7.5 through an increase in k(cat). A dose response demonstrated an EC50 of 52.7 mM total C(i) at pH 6.5. Slr1991 adenylyl cyclase was activated by CO2, but not by HCO3-. CO2 regulation of adenylyl cyclase was conserved in the CyaB1 adenylyl cyclase of An...

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Transducing emotionality: the role of adenylyl cyclases.

p t a V arious psychiatric disorders, including depression, anxiety, and other mood disorders, as well as responses to addictive drugs, have been linked to malfunctions of receptors coupled to the cyclic adenosine monophosphate (AMP) second-messenger signaling system and/or malfunction of downstream mediators such as protein kinase A (PKA) and the transcription factor cyclic AMP response elemen...

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Isolation and Structure of Adenylyl Cyclases

and a cytoplasmic carboxy terminus of ~35 kDa (C2) (FIGURE 1B). The catalytic domain of adenylyl cyclases is hypothesized to be bipartite and split between C1 and C2 regions. The predicted size of mammalian adenylyl cyclases ranges from 110 to 130 kDa, but these proteins generally have an apparent molecular weight on SDS gels of ~200 kDa due to glycosylation in the extracellular loops of M1 and...

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Ciliary adenylyl cyclases control the Hedgehog pathway.

Protein kinase A (PKA) accumulates at the base of the cilium where it negatively regulates the Hedgehog (Hh) pathway. Although PKA activity is essentially controlled by the cAMP produced by adenylyl cyclases, the influence of these enzymes on the Hh pathway remains unclear. Here, we show that adenylyl cyclase 5 and adenylyl cyclase 6 (AC5 and AC6, also known as ADCY5 and ADCY6, respectively) ar...

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ژورنال

عنوان ژورنال: Trends in Pharmacological Sciences

سال: 2012

ISSN: 0165-6147

DOI: 10.1016/j.tips.2011.10.006