scholarly journals Cyclic Adenosine Monophosphate and Brain-Derived Neurotrophic Factor Decreased Oxidative Stress and Apoptosis in Developing Hypothalamic Neuronal Cells: Role of Microglia

2013 ◽  
Vol 37 (8) ◽  
pp. 1370-1379 ◽  
Author(s):  
Nadka I. Boyadjieva ◽  
Dipak K. Sarkar
Keyword(s):  
Oxidative Stress ◽  
Neurotrophic Factor ◽  
Neuronal Cells ◽  
Cyclic Adenosine Monophosphate ◽  
Adenosine Monophosphate ◽  
Brain Derived Neurotrophic Factor

Possible Role of Oxidative Stress and Brain Derived Neurotrophic Factor in Triazophos Induced Cognitive Impairment in Rats

2013 ◽  
Vol 38 (10) ◽  
pp. 2136-2147 ◽  
Author(s):  
Smita Jain ◽  
Basu Dev Banerjee ◽  
Rafat Sultana Ahmed ◽  
Vinod Kumar Arora ◽  
Pramod Kumari Mediratta
Keyword(s):  
Oxidative Stress ◽  
Cognitive Impairment ◽  
Neurotrophic Factor ◽  
Brain Derived Neurotrophic Factor

Mechanisms of ATP to cAMP Conversion Catalyzed by the Mammalian Adenylyl Cyclase: A Role of Magnesium Coordination Shells and Proton Wires

2019 ◽  
Author(s):  
Bella Grigorenko ◽  
Igor Polyakov ◽  
Alexander Nemukhin
Keyword(s):  
Adenylyl Cyclase ◽  
Bond Cleavage ◽  
Cyclic Adenosine Monophosphate ◽  
Adenosine Monophosphate ◽  
Md Simulations ◽  
Coordination Shell ◽  
Energy Profile ◽  
One Step ◽  
Type V

<p>We report a mechanism of adenosine triphosphate (ATP) to cyclic adenosine monophosphate (cAMP) conversion by the mammalian type V adenylyl cyclase revealed in molecular dynamics (MD) and quantum mechanics/molecular mechanics (QM/MM) simulations. We characterize a set of computationally derived enzyme-substrate (ES) structures showing an important role of coordination shells of magnesium ions in the solvent accessible active site. Several stable six-fold coordination shells of Mg<sub>A</sub><sup>2+ </sup>are observed in MD simulations of ES complexes. In the lowest energy ES conformation, the coordination shell of Mg<sub>A</sub><sup>2+ </sup>does not include the O<sub>δ1</sub> atom of the conserved Asp440 residue. Starting from this conformation, a one-step reaction mechanism is characterized which includes proton transfer from the ribose O<sup>3'</sup>H<sup>3' </sup>group in ATP to Asp440 via a shuttling water molecule and P<sup>A</sup>-O<sup>3A</sup> bond cleavage and O<sup>3'</sup>-P<sup>A</sup> bond formation. The energy profile of this route is consistent with the observed reaction kinetics. In a higher energy ES conformation, Mg<sub>A</sub><sup>2+</sup> is bound to the O<sub>δ1</sub>(Asp440) atom as suggested in the relevant crystal structure of the protein with a substrate analog. The computed energy profile initiated by this ES is characterized by higher energy expenses to complete the reaction. Consistently with experimental data, we show that the Asp440Ala mutant of the enzyme should exhibit a reduced but retained activity. All considered reaction pathways include proton wires from the O<sup>3'</sup>H<sup>3' </sup>group via shuttling water molecules. </p>

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