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Phosphodiesterases
Published in Peter Grunwald, Pharmaceutical Biocatalysis, 2020
Moritz Helmstädter, Manfred Schubert-Zsilavecz
Enzymes of the family of cyclic nucleotide phosphodiesterases (PDE) are known to catalyze the breakdown of cyclic cAMP and cGMP. Since cyclic nucleotides (cN) play a such a crucial role as second messengers, phosphodiesterases have a key role in modulating signal transduction in various cell types by regulating the cellular levels of cNs by controlling their rates of degradation (Bender, 2006) (Fig. 2.1). Dysfunctions in PDE activities are associated with asthma, erectile dysfunction (ED), chronic obstructive pulmonary disease (COPD), pulmonary arterial hypertension, a plethora of autoimmune diseases, infertility, hypertension, intermittent claudication, heart failure, schizophrenia, dementia, stroke and depression (Francis et al., 2011a; Maurice et al., 2014).
Metabolism of carcinogenic pyrrolizidine alkaloids and pyrrolizidine alkaloid N-oxides by rat primary hepatocytes generate the same characteristic DHP-DNA adducts
Published in Journal of Environmental Science and Health, Part C, 2021
Xiaobo He, Qingsu Xia, Qiang Shi, Peter P. Fu
Monocrotaline, retrorsine, retrorsine N-oxide, cysteine, glutathione (GSH), calf thymus DNA (sodium salt, type I), nuclease P1, micrococcal nuclease (MN), spleen phosphodiesterase (SPD), 2′-deoxyguanosine (dG), and 2′-deoxyadenosine (dA), 2β-nicotinamide adenine dinucleotide 2′-phosphate, reduced (NADPH) were purchased from the Sigma Chemical Co. (St. Louis, MO, USA). [15N5]dG and [15N5,13C10]dA were purchased from Cambridge Isotope Laboratories (Tewksbury, MA, USA). All chemicals used for the study were analyzed by HPLC and found to be >97% pure. All solvents used were HPLC or LC/MS grade. Dulbecco’s Modified Eagle’s Medium (DMEM), fetal bovine serum (FBS), phosphate buffered saline (PBS, pH 7.4), trypsin-EDTA, penicillin, and streptomycin were purchased from Life Technologies (Grand Island, NY, USA). Blood & Cell Culture DNA Kits were purchased from QIAGEN (Valencia, CA, USA).
Toxicity, monitoring and biodegradation of organophosphate pesticides: A review
Published in Critical Reviews in Environmental Science and Technology, 2019
Gurpreet Kaur Sidhu, Simranjeet Singh, Vijay Kumar, Daljeet Singh Dhanjal, Shivika Datta, Joginder Singh
Other genes such as methyl parathion degradation (mpd) genes follow the different OP degrading pathway which allows the degradation of chlorpyrifos, methyl paraoxon and methyl parathion. Very less number of microbes especially Serratia and Pseudomonas species, possess the ability to degrade and mineralize the OP compounds. Various strains of genus Pseudomonas sp. A3 has been documented which can completely mineralize methyl parathion (Mishra, Khan, & Pandey, 2017). The strain hydrolyzes the methyl-parathion to p-nitrophenol, which consequently gets degraded by 1,2,4-benzenetriol and hydroquinone to maleyl-acetate (Caspi et al., 2012). The mechanism for diethyl thiophosphate utilization is still unknown, even the activity of enzyme is same as diethyl phosphate phosphodiesterase observed in D. acidovorans (Tehara & Keasling, 2003).
DNA Binding, amelioration of oxidative stress, and molecular docking study of Zn(II) metal complex of a new Schiff base ligand
Published in Journal of Coordination Chemistry, 2018
Dipu Kumar Mishra, Uttam Kumar Singha, Ananya Das, Somit Dutta, Pallab Kar, Arnab Chakraborty, Arnab Sen, Biswajit Sinha
The synthesized Schiff base Zn(II) complex has interesting target partners. To better understand their interaction with the complex and to understand which compound has better interaction, we have conducted the molecular docking experiments. Tyrosyl-DNA phosphodiesterase 1 has the best binding affinity with the complex (Table 2). These enzymes have DNA repair capacity and catalyze different hydrolysis reactions in nucleotides. Moreover, it is seen earlier from DNA interaction study that the Zn(II) complex has different DNA binding and cleaving activity. So, a high affinity of magnitude -10.5 kcal/mol in Auto Dock environment confirms these previous claims. Then again, induced myeloid leukemia cell differentiation protein Mcl-1 has the second best binding affinity. This protein plays a major role in apoptotic regulations. It is already seen that apart from Mcl-1 protein different Bcl-2 family proteins has major activity with the synthesized Zn(II) complex. Proteins like Bcl-2-like protein 1, Apoptosis regulator Bcl-2, and Bcl-2-like protein 2 are all members of Bcl-2 family of proteins, and all have good binding affinity with the synthesized complex (Figure 9). The proteins of Bcl-2 family are all linked to carcinogenesis pathway. So it is confirmed that along from nucleotide interaction the synthesized Zn(II) complex has possible implications in carcinogenesis.