A QM/MM study of the phosphoryl transfer to the Kemptide substrate catalyzed by protein kinase A. The effect of the phosphorylation state of the protein on the mechanism

2011 ◽  
Vol 13 (2) ◽  
pp. 530-539 ◽  
Author(s):  
Manuel Montenegro ◽  
Mireia Garcia-Viloca ◽  
José M. Lluch ◽  
Àngels González-Lafont
Keyword(s):  
Protein Kinase ◽  
Protein Kinase A ◽  
Phosphoryl Transfer ◽  
Phosphorylation State ◽  
Kinase A

scholarly journals How a Second Mg2+ Ion Affects the Phosphoryl-Transfer Mechanism in a Protein Kinase: A Computational Study

ACS Catalysis ◽  
2020 ◽  
Vol 11 (1) ◽  
pp. 169-183
Author(s):  
Rodrigo Recabarren ◽  
Kirill Zinovjev ◽  
Iñaki Tuñón ◽  
Jans Alzate-Morales
Keyword(s):  
Protein Kinase ◽  
Protein Kinase A ◽  
Computational Study ◽  
Transfer Mechanism ◽  
Phosphoryl Transfer ◽  
Kinase A

scholarly journals Phosphoryl Transfer by Protein Kinase A Is Captured in a Crystal Lattice

2013 ◽  
Vol 135 (12) ◽  
pp. 4788-4798 ◽  
Author(s):  
Adam C. Bastidas ◽  
Michael S. Deal ◽  
Jon M. Steichen ◽  
Yurong Guo ◽  
Jian Wu ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Crystal Lattice ◽  
Protein Kinase A ◽  
Phosphoryl Transfer ◽  
Kinase A

scholarly journals Dysfunctional conformational dynamics of protein kinase A induced by a lethal mutant of phospholamban hinder phosphorylation

2015 ◽  
Vol 112 (12) ◽  
pp. 3716-3721 ◽  
Author(s):  
Jonggul Kim ◽  
Larry R. Masterson ◽  
Alessandro Cembran ◽  
Raffaello Verardi ◽  
Lei Shi ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Protein Kinase A ◽  
Conformational Dynamics ◽  
Catalytic Efficiency ◽  
Phosphoryl Transfer ◽  
Clear Understanding ◽  
Adrenergic Stimulation ◽  
Lethal Mutant ◽  
Dynamic Interplay ◽  
Kinase A

The dynamic interplay between kinases and substrates is crucial for the formation of catalytically committed complexes that enable phosphoryl transfer. However, a clear understanding on how substrates modulate kinase structural dynamics to control catalytic efficiency is still missing. Here, we used solution NMR spectroscopy to study the conformational dynamics of two complexes of the catalytic subunit of the cAMP-dependent protein kinase A with WT and R14 deletion phospholamban, a lethal human mutant linked to familial dilated cardiomyopathy. Phospholamban is a central regulator of heart muscle contractility, and its phosphorylation by protein kinase A constitutes a primary response to β-adrenergic stimulation. We found that the single deletion of arginine in phospholamban’s recognition sequence for the kinase reduces its binding affinity and dramatically reduces phosphorylation kinetics. Structurally, the mutant prevents the enzyme from adopting conformations and motions committed for catalysis, with concomitant reduction in catalytic efficiency. Overall, these results underscore the importance of a well-tuned structural and dynamic interplay between the kinase and its substrates to achieve physiological phosphorylation levels for proper Ca2+ signaling and normal cardiac function.

Benchmark calculations on models of the phosphoryl transfer reaction catalyzed by protein kinase A

2009 ◽  
Vol 124 (3-4) ◽  
pp. 197-215 ◽  
Author(s):  
Manuel Montenegro ◽  
Mireia Garcia-Viloca ◽  
Àngels González-Lafont ◽  
José M. Lluch
Keyword(s):  
Protein Kinase ◽  
Protein Kinase A ◽  
Transfer Reaction ◽  
Phosphoryl Transfer ◽  
Kinase A
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