Can cerium oxide serve as a phosphodiesterase-mimetic nanozyme?

2019 ◽  
Vol 6 (12) ◽  
pp. 3684-3698 ◽  
Author(s):  
Pavel Janoš ◽  
Jakub Ederer ◽  
Marek Došek ◽  
Jiří Štojdl ◽  
Jiří Henych ◽  
...  
Keyword(s):  
Cerium Oxide ◽  
Adenosine Triphosphate ◽  
Cyclic Adenosine Monophosphate ◽  
Adenosine Monophosphate ◽  
Phosphodiester Bonds

Nanoceria accelerates dramatically not only the dephosphorylation of energetically rich biomolecules such as adenosine triphosphate (ATP), but also the cleavage of highly resistant phosphodiester bonds in 3′,5′-cyclic adenosine monophosphate (cAMP).

scholarly journals Molecular Mechanism of Light-Induced Acceleration of the Adenosine Triphosphate Conversion to the Cyclic Adenosine Monophosphate Catalyzed by the Photoactivated Adenylyl Cyclase bPAC

2020 ◽  
Author(s):  
Alexander Nemukhin ◽  
Maria Khrenova ◽  
Anna M. Kulakova
Keyword(s):  
Molecular Dynamics ◽  
Molecular Dynamics Simulations ◽  
Adenylyl Cyclase ◽  
Adenosine Triphosphate ◽  
Catalytic Domain ◽  
Cyclic Adenosine Monophosphate ◽  
Adenosine Monophosphate ◽  
Bluf Domain ◽  
Dynamics Simulations ◽  
Photoactivated Adenylyl Cyclase

<p>We report the first computational characterization of an optogenetic system composed of two photosensing BLUF (<u>b</u>lue <u>l</u>ight sensor <u>u</u>sing <u>f</u>lavin adenine dinucleotide) domains and two catalytic adenylyl cyclase (AC) domains. Conversion of adenosine triphosphate (ATP) to cyclic adenosine monophosphate (cAMP) and pyrophosphate (PPi) catalyzed by ACs coupled with excitation in photosensing domains has emerged in the focus of modern optogenetic applications because of the request in photoregulated enzymes to modulate cellular concentrations of signaling messengers. The photoactivated adenylyl cyclase from the soil bacterium <i>Beggiatoa sp.</i> (bPAC) is an important model showing considerable increase of the ATP to cAMP conversion rate in the catalytic domain after the illumination of the BLUF domain. The 1 μs classical molecular dynamics simulations reveal that the activation of the BLUF domain leading to tautomerization of Gln49 in the chromophore binding pocket results in switching of position of the side chain of Arg278 in the active site of AC. Allosteric signal transmission pathways between Gln49 from BLUF and Arg278 from AC were revealed by the dynamical network analysis. The Gibbs energy profiles of the ATP → cAMP + PPi reaction computed using QM(DFT(ωB97X-D3/6-31G**))/MM(CHARMM) molecular dynamics simulations for both Arg278 conformations in AC clarify the reaction mechanism. In the light-activated system, the corresponding arginine conformation stabilizes the pentacoordinated phosphorus of the α-phosphate group in the transition state, thus lowering the activation energy. Simulations of the bPAC system with the Tyr7Phe replacement in BLUF demonstrate occurrence of both arginine conformations in an equal ratio, explaining the experimentally observed intermediate catalytic activity of the bPAC-Y7F variant as compared with the dark and light states of the wild type bPAC. </p>

scholarly journals Involvement of a cyclic adenosine monophosphate-dependent signal in the diet-induced canalicular trafficking of adenosine triphosphate-binding cassette transporter g5/g8

Hepatology ◽  
2015 ◽  
Vol 62 (4) ◽  
pp. 1215-1226 ◽  
Author(s):  
Yasuhiro Yamazaki ◽  
Kenta Yasui ◽  
Takahiro Hashizume ◽  
Arisa Suto ◽  
Ayaka Mori ◽  
...  
Keyword(s):  
Adenosine Triphosphate ◽  
Cyclic Adenosine Monophosphate ◽  
Adenosine Monophosphate ◽  
Dependent Signal

46 VITRIFICATION AT THE GERMINAL VESICLE STAGE TRIGGERS PRECOCIOUS MEIOTIC RESUMPTION BUT DOES NOT AFFECT CYTOPLASMIC MATURATION IN CUMULUS-ENCLOSED PORCINE OOCYTES DURING IN VITRO MATURATION

2016 ◽  
Vol 28 (2) ◽  
pp. 153
Author(s):  
T. Somfai ◽  
N. T. Men ◽  
H. Kaneko ◽  
J. Noguchi ◽  
S. Haraguchi ◽  
...  
Keyword(s):  
Adenosine Triphosphate ◽  
In Vitro Maturation ◽  
Germinal Vesicle ◽  
Cyclic Adenosine Monophosphate ◽  
Adenosine Monophosphate ◽  
Control Group ◽  
Control Groups ◽  
Porcine Oocyte ◽  
And Control

Previously we have reported a vitrification protocol that allows preservation of immature porcine oocytes in large numbers (Somfai et al. 2014 PLoS One 9, e97731). However, despite high survival rates, embryo development rates have remained low. The aim of our current research is to reveal factors potentially responsible for reduced developmental competence of vitrified oocytes. As a first step, we investigated the effects of vitrification at the germinal vesicle stage on subsequent nuclear progression and the normality of cytoplasmic functions during in vitro maturation (IVM). Cumulus-enclosed porcine oocytes were vitrified in microdrops, stored, and then warmed by our method (Somfai et al. 2015 Reprod. Fertil. Dev. 27, 124). Then the oocytes were subjected to IVM for 46 h in a chemically defined porcine oocyte medium. During the first 22 h of IVM, the medium was supplemented with 1 mM dibutyryl cyclic adenosine monophosphate, 10 IU mL–1 of eCG, and 10 IU mL–1 of hCG. The following 24 h of IVM was performed in porcine oocyte medium without any supplementation. We compared vitrified/warmed oocytes (vitrified group) with freshly collected immature oocytes (control group) in terms of (1) nuclear progression, (2) intracellular glutathione (GSH), and (3) adenosine triphosphate levels throughout IVM. Each experiment was replicated at least 3 times. Results were analysed by one-way ANOVA and Tukey’s multiple comparison test. A total of 510 oocytes were vitrified of which 422 (82.3%) survived. Only live oocytes were subjected to subsequent assays. Orcein staining revealed that after 22 h of IVM, a significantly higher percentage (P < 0.05) of vitrified oocytes showed germinal vesicle breakdown compared with the control group (22.0 v. 0.9%, respectively). In a similar fashion, after 30 h IVM, a significantly higher (P < 0.05) percentage of oocytes reached the metaphase-II (MII) stage in the vitrified group than in the control group (21.8 v. 0%, respectively). After 46 h of IVM, there was no difference between the vitrified and control groups in terms of the percentage of MII stage oocytes (93.9 and 86.3%, respectively). Analysis of GSH levels in oocytes by the 5,5′-dithio-bis-2-nitrobenzoic acid-glutathione disulfide reductase recycling assay showed no significant difference between the vitrified and control groups at 0 h (6.7 and 7.0 pmol, respectively), 22 h (5.5 and 5.5 pmol, respectively), and 46 h (6.9 and 7.9 pmol, respectively) of IVM. Adenosine triphosphate assay (FL-ASC; Sigma-Aldrich Co., St. Louis, MO) revealed similar adenosine triphosphate contents in the oocytes of the vitrified and control groups at 0 h (1.53 and 1.61 pmol, respectively), 22 h (1.67 and 1.70 pmol, respectively), and 46 h (1.65 and 1.83 pmol, respectively) of IVM. In conclusion, vitrification triggered precocious nuclear maturation even in the presence of dibutyryl cyclic adenosine monophosphate; however, it did not affect GSH levels and overall metabolism. This work was supported by JSPS KAKENHI (Grant Number: 26870839) and JST/JICA SATREPS.

scholarly journals Allosteric inhibition of adenylyl cyclase type 5 by G-protein: a molecular dynamics study

2020 ◽  
Author(s):  
Elisa Frezza ◽  
Tina-Méryl Amans ◽  
Juliette Martin
Keyword(s):  
Molecular Dynamics ◽  
Adenylyl Cyclase ◽  
G Protein ◽  
Adenosine Triphosphate ◽  
Crucial Role ◽  
Protein A ◽  
Cyclic Adenosine Monophosphate ◽  
Structural Data ◽  
Adenosine Monophosphate ◽  
Protein Subunit

AbstractAdenylyl cyclases (ACs) have a crucial role in many signal transduction pathways, in particular in the intricate control of cyclic AMP (cAMP) generation from adenosine triphosphate (ATP). Using homology models developed from existing structural data and docking experiments, we have carried out all-atom, microsecond-scale molecular dynamics simulations on the AC5 isoform of adenylyl cyclase bound to the inhibitory G-protein subunit Gαi in the presence and in the absence of ATP. The results show that Gαi have significant effects on the structure and flexibility of adenylyl cyclase, as observed earlier for the binding of ATP and Gsα. New data on Gαi bound to the C1 domain of AC5 help to explain how Gαi inhibits enzyme activity and to get insight on its regulation. Simulations also suggest a crucial role of ATP in the regulation of stimulation and inhibition of AC5.Author summaryThe neurons that compose the human brain are able to respond to multiple inputs from other neurons. The chemical “integration” of these inputs then decides whether a given neuron passes on a signal or not. External chemical messages act on neurons via proteins in their membranes that trigger cascades of reactions within the cell. One key molecule in these signaling cascades is cyclic adenosine monophosphate (cAMP) that is chemically synthesized from adenosine triphosphate (ATP) by the enzyme adenylyl cyclase (AC). We are investigating the mechanisms that control how much cAMP is produced as a function of the signals received by the neuron. In particular, we have studied the inhibition effect of a key protein, termed Gαi, on AC, and we compare it with the stimulator effect of another key protein termed Gsα. Using microsecond molecular simulations, we have been able to show how binding Gαi to AC changes its structure and its dynamics so that its enzymatic activity is quenched and that ATP seems to have a crucial role in the regulation of stimulation and inhibition of AC5.

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