scholarly journals Activation of PKA via asymmetric allosteric coupling of structurally conserved cyclic nucleotide binding domains

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Yuxin Hao ◽  
Jeneffer P. England ◽  
Luca Bellucci ◽  
Emanuele Paci ◽  
H. Courtney Hodges ◽  
...  
Keyword(s):  
Cyclic Nucleotide ◽  
Nucleotide Binding ◽  
Cyclic Nucleotide Binding ◽  
Allosteric Coupling ◽  
Binding Domains

scholarly journals Identification of a Novel Type of cGMP Phosphodiesterase That Is Defective in the ChemotacticstmFMutants

2002 ◽  
Vol 13 (11) ◽  
pp. 3870-3877 ◽  
Author(s):  
Marcel E. Meima ◽  
Ricardo M. Biondi ◽  
Pauline Schaap
Keyword(s):  
Fusion Protein ◽  
Cyclic Nucleotide ◽  
Nucleotide Binding ◽  
Cyclic Nucleotide Binding ◽  
Cgmp Phosphodiesterase ◽  
Novel Gene ◽  
Binding Domains ◽  
Null Mutants

StmF mutants are chemotactic mutants that are defective in a cGMP phosphodiesterase (PDE) activity. We identified a novel gene, PdeD, that harbors two cyclic nucleotide–binding domains and a metallo-β-lactamase homology domain. Similar to stmF mutants,pdeD-null mutants displayed extensively streaming aggregates, prolonged elevation of cGMP levels after chemotactic stimulation, and reduced cGMP-PDE activity. PdeDtranscripts were lacking in stmF mutant NP377, indicating that this mutant carries a PdeD lesion. Expression of a PdeD-YFP fusion protein in pdeD-null cells restored the normal cGMP response and showed that PdeD resides in the cytosol. When purified by immunoprecipitation, the PdeD-YFP fusion protein displayed cGMP-PDE activity, which was retained in a truncated construct that contained only the metallo-β-lactamase domain.

scholarly journals Dynamically Driven Ligand Selectivity in Cyclic Nucleotide Binding Domains

2009 ◽  
Vol 284 (35) ◽  
pp. 23682-23696 ◽  
Author(s):  
Rahul Das ◽  
Somenath Chowdhury ◽  
Mohammad T. Mazhab-Jafari ◽  
Soumita SilDas ◽  
Rajeevan Selvaratnam ◽  
...  
Keyword(s):  
Cyclic Nucleotide ◽  
Nucleotide Binding ◽  
Cyclic Nucleotide Binding ◽  
Ligand Selectivity ◽  
Binding Domains

scholarly journals Towards Revealing a Cooperative Mechanism of Camp Binding to HCN2 Cyclic Nucleotide Binding Domains at the Single-Molecule Level

2018 ◽  
Vol 114 (3) ◽  
pp. 120a
Author(s):  
David S. White ◽  
Marcel P. Goldschen-Ohm ◽  
Ruohan Zhang ◽  
Vadim A. Klenchin ◽  
Randall H. Goldsmith ◽  
...  
Keyword(s):  
Single Molecule ◽  
Cyclic Nucleotide ◽  
Nucleotide Binding ◽  
Cyclic Nucleotide Binding ◽  
Single Molecule Level ◽  
Binding Domains

scholarly journals Identification and Characterization of Two Unusual cGMP-stimulated Phoshodiesterases in Dictyostelium

2002 ◽  
Vol 13 (11) ◽  
pp. 3878-3889 ◽  
Author(s):  
Leonard Bosgraaf ◽  
Henk Russcher ◽  
Helena Snippe ◽  
Sonya Bader ◽  
Joyce Wind ◽  
...  
Keyword(s):  
Cyclic Nucleotide ◽  
Catalytic Domain ◽  
Nucleotide Binding ◽  
Biochemical Properties ◽  
Cyclic Nucleotide Binding ◽  
Cgmp Phosphodiesterase ◽  
Binding Domains ◽  
Dual Specificity ◽  
Camp Levels

Recently, we recognized two genes, gbpA andgbpB, encoding putative cGMP-binding proteins with a Zn2+-hydrolase domain and two cyclic nucleotide binding domains. The Zn2+-hydrolase domains belong to the superfamily of β-lactamases, also harboring a small family of class II phosphodiesterases from bacteria and lower eukaryotes. Gene inactivation and overexpression studies demonstrate thatgbpA encodes the cGMP-stimulated cGMP-phosphodiesterase that was characterized biochemically previously and was 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 seems to encode a dual specificity phosphodiesterase with preference for cAMP. The enzyme hydrolyses cAMP ∼9-fold faster than cGMP and is activated by cAMP and cGMP with aK A value of ∼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, whereas the cyclic nucleotide binding 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.

scholarly journals Structural snapshot of cyclic nucleotide binding domains from cyclic nucleotide-sensitive ion channels

2013 ◽  
Vol 394 (11) ◽  
pp. 1439-1451 ◽  
Author(s):  
Sven Schünke ◽  
Matthias Stoldt
Keyword(s):  
Conformational Changes ◽  
Cyclic Nucleotide ◽  
Signal Amplification ◽  
Nucleotide Binding ◽  
Detailed Mechanism ◽  
Channel Pore ◽  
Cyclic Nucleotide Binding ◽  
Channel Proteins ◽  
Binding Domains ◽  
Structural Insights

Abstract Cyclic nucleotide-binding domains (CNBDs) that are present in various channel proteins play crucial roles in signal amplification cascades. Although atomic resolution structures of some of those CNBDs are available, the detailed mechanism by which they confer cyclic nucleotide-binding to the ion channel pore remains poorly understood. In this review, we describe structural insights about cyclic nucleotide-binding-induced conformational changes in CNBDs and their potential coupling with channel gating.

Sign in / Sign up

Export Citation Format

Share Document