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The Regulatory Tandem Domains of Human Phosphodiesterases 1 and 4 Regulate a Cyanobacterial Adenylyl Cyclase

The Regulatory Tandem Domains of Human Phosphodiesterases 1 and 4 Regulate a Cyanobacterial Adenylyl Cyclase

Ana Banjac, Ursula Kurz, Joachim E Schultz

Cell Signal. 2012 Aug;24(8):1479-84.

PMID: 22484154

Abstract:

Human phosphodiesterase 1 is regulated by a tandem of N-terminal calmodulin/Ca(2+)-binding domains. We grafted the tandems from hPDE1A3 and -B1 onto the cyanobacterial adenylyl cyclase CyaB1 thus replacing an intrinsic tandem GAF-domain. Cyclase activity was stimulated by Ca(2+)/calmodulin 1.9 to 4.4-fold, i.e. similarly as reported for hPDE1 regulation. hPDE4 long isoforms are activated by phosphorylation of a serine located in a conserved RRESF motif in a tandem of N-terminal upstream-conserved regions (UCR). We grafted the UCR tandems from hPDE4A4, -B1, and -D3 onto the CyaB1 cyclase as a reporter enzyme. Activity was enhanced 1.4 to 4.5-fold by respective phosphomimetic (S/D) point mutations. Similarly, cyclase activity was increased 2.5-fold by phosphorylation of the chimera with the PDE4D3 UCR tandem by cAMP-dependent protein kinase. We propose a common mechanism of activation in mammalian phosphodiesterases containing N-terminal tandem regulatory domains. A downstream region is suggested to alternate between random and ordered conformations and to enable switching between inactive, the catalytic domain occluding PDE homodimers and active monomeric PDE catalytic domains.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
IAR4245705	PDE4D3 Active human			Price

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