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A more recent version of this article appeared on November 1, 2002
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Submitted on May 27, 2002
Revised on July 30, 2002
Accepted on August 19, 2002
1 Department of Biochemistry, University of Groningen, Nijenborgh 4, 9747 AG Groningen, the Netherlands
* Corresponding author. E-mail address: P.J.M.van.Haastert{at}chem.rug.nl.
Recently we recognized two genes, gbpA and gbpB, encoding putative cGMP-binding proteins with a Zn2+-hydrolase domain and two cyclic nucleotide binding (cNB) domains. The Zn2+-hydrolase domains belong to the superfamily of beta-lactamases, also harboring a small family of class II phosphodiesterases from bacteria and lower eukaryotes. Gene inactivation and overexpression studies demonstrate that gbpA encodes the cGMP-stimulated cGMP-phosphodiesterase that was characterized biochemically previously, and shown to be involved in chemotaxis. cAMP neither activates nor is a substrate of GbpA. The gbpB gene is expressed mainly in the multicellular stage and appears to encode a dual specificity phosphodiesterase with preference for cAMP. The enzyme hydrolyses cAMP about 9-fold faster than cGMP, and is activated by cAMP and cGMP with a Ka of about 0.7 and 2.3 µM, respectively. Cells with a deletion of the gbpB gene have increased basal and receptor stimulated cAMP levels, and are sporogeneous. We propose that GbpA and GbpB hydrolyze the substrate in the Zn2+-hydrolase domain, while the cNB domains mediate activation. The human cGMP-stimulated cAMP/cGMP phosphodiesterase has similar biochemical properties, but a completely different topology: hydrolysis takes place by a class I catalytic domain and GAF domains mediate cGMP-activation.
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