scholarly journals Switching Cyclic Nucleotide-Selective Activation of Cyclic Adenosine Monophosphate-Dependent Protein Kinase Holoenzyme Reveals Distinct Roles of Tandem Cyclic Nucleotide-Binding Domains

2017 ◽  
Vol 12 (12) ◽  
pp. 3057-3066 ◽  
Author(s):  
Daniel He ◽  
Robin Lorenz ◽  
Choel Kim ◽  
Friedrich W. Herberg ◽  
Chinten James Lim
Keyword(s):  
Protein Kinase ◽  
Cyclic Nucleotide ◽  
Cyclic Adenosine Monophosphate ◽  
Adenosine Monophosphate ◽  
Nucleotide Binding ◽  
Selective Activation ◽  
Dependent Protein Kinase ◽  
Cyclic Nucleotide Binding ◽  
Binding Domains ◽  
Dependent Protein

scholarly journals Mutations that prevent cyclic nucleotide binding to binding sites A or B of type I cyclic AMP-dependent protein kinase.

1988 ◽  
Vol 263 (33) ◽  
pp. 17397-17404
Author(s):  
D Ogreid ◽  
S O Døskeland ◽  
K B Gorman ◽  
R A Steinberg
Keyword(s):  
Protein Kinase ◽  
Cyclic Amp ◽  
Cyclic Nucleotide ◽  
Binding Sites ◽  
Nucleotide Binding ◽  
Type I ◽  
Dependent Protein Kinase ◽  
Cyclic Nucleotide Binding ◽  
Dependent Protein

scholarly journals Mutations of PKA cyclic nucleotide-binding domains reveal novel aspects of cyclic nucleotide selectivity

2017 ◽  
Vol 474 (14) ◽  
pp. 2389-2403 ◽  
Author(s):  
Robin Lorenz ◽  
Eui-Whan Moon ◽  
Jeong Joo Kim ◽  
Sven H. Schmidt ◽  
Banumathi Sankaran ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Cyclic Nucleotide ◽  
Molecular Basis ◽  
Nucleotide Binding ◽  
Effector Proteins ◽  
Regulatory Subunit ◽  
Dependent Protein Kinase ◽  
Cyclic Nucleotide Binding ◽  
Arginine Residues ◽  
Dependent Protein

Cyclic AMP and cyclic GMP are ubiquitous second messengers that regulate the activity of effector proteins in all forms of life. The main effector proteins, the 3′,5′-cyclic adenosine monophosphate (cAMP)-dependent protein kinase (PKA) and the 3′,5′-cyclic guanosine monophosphate (cGMP)-dependent protein kinase (PKG), are preferentially activated by cAMP and cGMP, respectively. However, the molecular basis of this cyclic nucleotide selectivity is still not fully understood. Analysis of isolated cyclic nucleotide-binding (CNB) domains of PKA regulatory subunit type Iα (RIα) reveals that the C-terminal CNB-B has a higher cAMP affinity and selectivity than the N-terminal CNB-A. Here, we show that introducing cGMP-specific residues using site-directed mutagenesis reduces the selectivity of CNB-B, while the combination of two mutations (G316R/A336T) results in a cGMP-selective binding domain. Furthermore, introducing the corresponding mutations (T192R/A212T) into the PKA RIα CNB-A turns this domain into a highly cGMP-selective domain, underlining the importance of these contacts for achieving cGMP specificity. Binding data with the generic purine nucleotide 3′,5′-cyclic inosine monophosphate (cIMP) reveal that introduced arginine residues interact with the position 6 oxygen of the nucleobase. Co-crystal structures of an isolated CNB-B G316R/A336T double mutant with either cAMP or cGMP reveal that the introduced threonine and arginine residues maintain their conserved contacts as seen in PKG I CNB-B. These results improve our understanding of cyclic nucleotide binding and the molecular basis of cyclic nucleotide specificity.

Mapping of the two intrachain cyclic nucleotide binding sites of adenosine cyclic 3',5'-phosphate dependent protein kinase I

Biochemistry ◽  
1983 ◽  
Vol 22 (5) ◽  
pp. 1094-1101 ◽  
Author(s):  
Stein O. Doeskeland ◽  
Dagfinn Oegreid ◽  
Roald Ekanger ◽  
Priscilla A. Sturm ◽  
Jon P. Miller ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Cyclic Nucleotide ◽  
Binding Sites ◽  
Nucleotide Binding ◽  
Dependent Protein Kinase ◽  
Cyclic Nucleotide Binding ◽  
Nucleotide Binding Sites ◽  
Dependent Protein

scholarly journals Crystal structure of cGMP-dependent protein kinase Iβ cyclic nucleotide-binding-B domain : Rp-cGMPS complex reveals an apo-like, inactive conformation

FEBS Letters ◽  
2016 ◽  
Vol 591 (1) ◽  
pp. 221-230 ◽  
Author(s):  
James C. Campbell ◽  
Bryan VanSchouwen ◽  
Robin Lorenz ◽  
Banumathi Sankaran ◽  
Friedrich W. Herberg ◽  
...  
Keyword(s):  
Crystal Structure ◽  
Protein Kinase ◽  
Cyclic Nucleotide ◽  
Nucleotide Binding ◽  
Dependent Protein Kinase ◽  
Inactive Conformation ◽  
Cyclic Nucleotide Binding ◽  
Cgmp Dependent Protein Kinase ◽  
Dependent Protein
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