cAMP Is a Ligand for the Tandem GAF Domain of Human Phosphodiesterase 10 and cGMP for the Tandem GAF Domain of Phosphodiesterase 11
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چکیده
منابع مشابه
Modeling and mutational analysis of the GAF domain of the cGMP-binding, cGMP-specific phosphodiesterase, PDE5.
The GAFa domain of the cGMP-binding, cGMP-specific phosphodiesterase (PDE5A) was modeled on the crystal structure of PDE2A GAF domain and residues involved in cGMP binding identified. Tandem GAFa and GAFb domains of PDE5A, expressed in Escherichia coli, bound cGMP (K(d) 27 nM). Mutation of aspartate-299 in GAFa, suggested earlier to be critical for cGMP binding, did not abrogate cGMP binding, b...
متن کاملThe structure of the GAF A domain from phosphodiesterase 6C reveals determinants of cGMP binding, a conserved binding surface, and a large cGMP-dependent conformational change.
The photoreceptor phosphodiesterase (PDE6) regulates the intracellular levels of the second messenger cGMP in the outer segments of cone and rod photoreceptor cells. PDE6 contains two regulatory GAF domains, of which one (GAF A) binds cGMP and regulates the activity of the PDE6 holoenzyme. To increase our understanding of this allosteric regulation mechanism, we present the 2.6A crystal structu...
متن کاملThe two GAF domains in phosphodiesterase 2A have distinct roles in dimerization and in cGMP binding.
Cyclic nucleotide phosphodiesterases (PDEs) regulate all pathways that use cGMP or cAMP as a second messenger. Five of the 11 PDE families have regulatory segments containing GAF domains, 3 of which are known to bind cGMP. In PDE2 binding of cGMP to the GAF domain causes an activation of the catalytic activity by a mechanism that apparently is shared even in the adenylyl cyclase of Anabaena, an...
متن کاملA 46-amino acid segment in phosphodiesterase-5 GAF-B domain provides for high vardenafil potency over sildenafil and tadalafil and is involved in phosphodiesterase-5 dimerization.
Phosphodiesterase-5 (PDE5) contains a catalytic domain (C domain) that hydrolyzes cGMP and a regulatory domain (R domain) that contains two mammalian cGMP-binding phosphodiesterase, Anabaena adenylyl cyclases, Escherichia coli FhlAs (GAFs) (A and B) and a phosphorylation site for cyclic nucleotide-dependent protein kinases (cNPKs). Binding of cGMP to GAF-A increases cNPK phosphorylation of PDE5...
متن کاملBinding of cyclic nucleotides to phosphodiesterase 10A and 11A GAF domains does not stimulate catalytic activity.
To date eleven human PDE (3',5'-cyclic nucleotide phosphodiesterase) families have been identified. Of these, five families contain non-catalytic tandem GAF (cGMP-specific and -stimulated phosphodiesterases, Anabaena adenylate cyclases and Escherichia coli FhlA) domains, GAFa and GAFb, in the N-terminal part of the enzyme. For PDE2A, PDE5A and PDE6 the GAF domains have been shown to bind cGMP w...
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ژورنال
عنوان ژورنال: Journal of Biological Chemistry
سال: 2006
ISSN: 0021-9258
DOI: 10.1074/jbc.m511468200