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Determining Redox Potentials of the Iron-Sulfur Clusters of the AdoMet Radical Enzyme Superfamily.
Maiocco, SJ, Walker, LM, Elliott, SJ
Methods in enzymology. 2018;:319-339
Abstract
While protein film electrochemistry (PFE) has proven to be an effective tool in the interrogation of redox cofactors and assessing the electrocatalytic activity of many different enzymes, recently it has been proven to be useful for the study of the redox potentials of the cofactors of AdoMet radical enzymes (AREs). In this chapter, we review the challenges and opportunities of examining the redox cofactors of AREs in a high level of detail, particularly for the deconvolution of redox potentials of multiple cofactors. We comment on how to best assess the electroactive nature of any given ARE, and we see that when applied well, PFE allows for not only determining redox potentials, but also determining proton-coupling and ligand-binding phenomena in the ARE superfamily.
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Enzymatic Mechanisms Involved in Evasion of Fungi to the Oxidative Stress: Focus on Scedosporium apiospermum.
Staerck, C, Vandeputte, P, Gastebois, A, Calenda, A, Giraud, S, Papon, N, Bouchara, JP, Fleury, MJJ
Mycopathologia. 2018;(1):227-239
Abstract
The airways of patients with cystic fibrosis (CF) are frequently colonized by various filamentous fungi, mainly Aspergillus fumigatus and Scedosporium species. To establish within the respiratory tract and cause an infection, these opportunistic fungi express pathogenic factors allowing adherence to the host tissues, uptake of extracellular iron, or evasion to the host immune response. During the colonization process, inhaled conidia and the subsequent hyphae are exposed to reactive oxygen species (ROS) and reactive nitrogen species (RNS) released by phagocytic cells, which cause in the fungal cells an oxidative stress and a nitrosative stress, respectively. To cope with these constraints, fungal pathogens have developed various mechanisms that protect the fungus against ROS and RNS, including enzymatic antioxidant systems. In this review, we summarize the different works performed on ROS- and RNS-detoxifying enzymes in fungi commonly encountered in the airways of CF patients and highlight their role in pathogenesis of the airway colonization or respiratory infections. The potential of these enzymes as serodiagnostic tools is also emphasized. In addition, taking advantage of the recent availability of the whole genome sequence of S. apiospermum, we identified the various genes encoding ROS- and RNS-detoxifying enzymes, which pave the way for future investigations on the role of these enzymes in pathogenesis of these emerging species since they may constitute new therapeutics targets.
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3.
Thermodynamic Activity-Based Progress Curve Analysis in Enzyme Kinetics.
Pleiss, J
Trends in biotechnology. 2018;(3):234-238
Abstract
Macrokinetic Michaelis-Menten models based on thermodynamic activity provide insights into enzyme kinetics because they separate substrate-enzyme from substrate-solvent interactions. Kinetic parameters are estimated from experimental progress curves of enzyme-catalyzed reactions. Three pitfalls are discussed: deviations between thermodynamic and concentration-based models, product effects on the substrate activity coefficient, and product inhibition.
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4.
Enzymes: Plant-based Production and their Applications.
Khan, MS, Mustafa, G, Joyia, FA
Protein and peptide letters. 2018;(2):136-147
Abstract
BACKGROUND Enzymes are biocatalysts that play key roles in the production of biomolecules. Transgenic plants can be valuable cost effective resource to produce enzymes with bona fide structure. Further, plants provide inexpensive production platforms for pharmaceuticals and nutraceuticals. OBJECTIVE This review article summarizes the properties and importance of enzymes and describes how foreign proteins/enzymes accumulate in plant cells that can be used for commercial purposes. CONCLUSION The instances illustrated in this review evidently depict that plant enzymes involved in fundamental cellular activities are of great importance regarding plant growth and development. Investigating these enzymes and the metabolic pathways involved in their synthesis will certainly help to improve plant and human health. Furthermore, enzymes of industrial and pharmaceutical importance can be expressed in genetically modified plants to obtain enhanced expression. Considering easiness of obtaining desired expression, GM plants can offer a good alternate for large scale production of enzymes.
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5.
Oxidation catalysis by iron and manganese porphyrins within enzyme-like cages.
Chino, M, Leone, L, Zambrano, G, Pirro, F, D'Alonzo, D, Firpo, V, Aref, D, Lista, L, Maglio, O, Nastri, F, et al
Biopolymers. 2018;(10):e23107
Abstract
Inspired by natural heme-proteins, scientists have attempted for decades to design efficient and selective metalloporphyrin-based oxidation catalysts. Starting from the pioneering work on small molecule mimics in the late 1970s, we have assisted to a tremendous progress in designing cages of different nature and complexity, able to accommodate metalloporphyrins. With the intent of tuning and controlling their reactivity, more and more sophisticated and diverse environments are continuously exploited. In this review, we will survey the current state of art in oxidation catalysis using iron- and manganese-porphyrins housed within designed or engineered protein cages. We will also examine the innovative metal-organic framework (MOF) systems, exploited to achieving an enzyme-like environment around the metalloporphyrin cofactor.
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Postprandial effects of wine consumption on Platelet Activating Factor metabolic enzymes.
Argyrou, C, Vlachogianni, I, Stamatakis, G, Demopoulos, CA, Antonopoulou, S, Fragopoulou, E
Prostaglandins & other lipid mediators. 2017;:23-29
Abstract
Platelet Activating factor (PAF) is a potent inflammatory mediator that is involved in the initiation and the prolongation of atherosclerosis. The purpose of the study was to investigate the effect of wine consumption on the activity of PAF metabolic enzymes and on IL-6 levels as a cytokine inflammatory marker. Healthy men participated in 4 daily trials and consumed a standardized meal along with Robola wine (trial R), or Cabernet Sauvignon (trial CS), or ethanol solution (trial E), or water (trial W). A significant trial effect was found in the activity of lyso-PAF acetyltransferase (Lyso-PAF AT) (ptrial=0.01). In specific, R trial decreased enzyme activity compared to E trial (p=0.03) while a trend for differentiation was observed between CS trial and E one (p=0.06) as well as between R trial and W one (p=0.07). Concerning PAF-cholinephosphotransferase (PAF-CPT) activity, a significant trial effect was found (ptrial<0.00). Specifically, both R (p=0.002) and CS (p=0.001) trials decreased enzyme activity compared to E trial. Concerning lipoprotein-associated phospholipase A2 (LpPLA2) no time either trial effect was observed. Concerning IL-6 levels a significant time effect was found (ptime<0.00) while no trial effect was revealed. In conclusion, the protective effect of wine consumption could partly be explained through the modulation of PAF metabolism by wine micro-constituents that lead to lower PAF levels.
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7.
Mechanistic Understanding of Lanthipeptide Biosynthetic Enzymes.
Repka, LM, Chekan, JR, Nair, SK, van der Donk, WA
Chemical reviews. 2017;(8):5457-5520
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Abstract
Lanthipeptides are ribosomally synthesized and post-translationally modified peptides (RiPPs) that display a wide variety of biological activities, from antimicrobial to antiallodynic. Lanthipeptides that display antimicrobial activity are called lantibiotics. The post-translational modification reactions of lanthipeptides include dehydration of Ser and Thr residues to dehydroalanine and dehydrobutyrine, a transformation that is carried out in three unique ways in different classes of lanthipeptides. In a cyclization process, Cys residues then attack the dehydrated residues to generate the lanthionine and methyllanthionine thioether cross-linked amino acids from which lanthipeptides derive their name. The resulting polycyclic peptides have constrained conformations that confer their biological activities. After installation of the characteristic thioether cross-links, tailoring enzymes introduce additional post-translational modifications that are unique to each lanthipeptide and that fine-tune their activities and/or stability. This review focuses on studies published over the past decade that have provided much insight into the mechanisms of the enzymes that carry out the post-translational modifications.
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The role of vitamin C in epigenetic regulation.
Guz, J, Oliński, R
Postepy higieny i medycyny doswiadczalnej (Online). 2017;(1):747-760
Abstract
Vitamin C (L-ascorbic acid) is a micronutrient best known for its anti-scurvy activity in humans. Vitamin C is involved in many biological processes involving enzymatic reactions that are catalyzed by members of dioxygenases which use Fe(II) and 2-oxoglutarate as a co-substrate.The article reviews recent data that suggest the involvement of ascorbate in dioxygenases catalyzed chromatin and DNA modifications which thereby contribute to epigenetic regulation. Concerning chromatin modification, the dioxygenases are involved in distinct demethylation reactions with varying specificity for the position of the lysine on the target histone. TET hydroxylases catalyse the oxidation of methyl groups in the 5 position of cytosine in DNA yielding 5-hydroxymethylcytosine, while further iterative oxidation reactions results in the formation of 5-formylcytosine and 5-carboxylcytosine. A few previous studies demonstrated that ascorbate may enhance generation of 5-hydroxymethylcytosine in cultured cells, probably acting as a cofactor of TETs during hydroxylation of 5-methylcytosine. Physiological concentrations of ascorbate in human serum (10-100 μM) may guarantee stable level of 5-hydroxymethylcytosine, a modification necessary for epigenetic function of the cell. 5-Hydroxymethylcytosine level is substantially decreased in almost all investigated cancers, what may be linked with cancer development. Therefore, it is possible that supplementation with ascorbate could contribute to better management of individual cancer patient. This issue is also discussed in our paper.
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Synthesis and biological applications of fluoro-modified nucleic acids.
Guo, F, Li, Q, Zhou, C
Organic & biomolecular chemistry. 2017;(45):9552-9565
Abstract
Owing to the unique physical properties of a fluorine atom, incorporating fluoro-modifications into nucleic acids offers striking biophysical and biochemical features, and thus significantly extends the breadth and depth of biological applications of nucleic acids. In this review, fluoro-modified nucleic acids that have been synthesized through either solid phase synthesis or the enzymatic approach are briefly summarised, followed by a section describing their biomedical applications in nucleic acid-based therapeutics, 18F PET imaging and mechanistic studies of DNA modifying enzymes. In the last part, the utility of 19F NMR and MRI for probing the structure, dynamics and molecular interactions of fluorinated nucleic acids is reviewed.
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10.
Enzymatic Halogenation and Dehalogenation Reactions: Pervasive and Mechanistically Diverse.
Agarwal, V, Miles, ZD, Winter, JM, Eustáquio, AS, El Gamal, AA, Moore, BS
Chemical reviews. 2017;(8):5619-5674
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Abstract
Naturally produced halogenated compounds are ubiquitous across all domains of life where they perform a multitude of biological functions and adopt a diversity of chemical structures. Accordingly, a diverse collection of enzyme catalysts to install and remove halogens from organic scaffolds has evolved in nature. Accounting for the different chemical properties of the four halogen atoms (fluorine, chlorine, bromine, and iodine) and the diversity and chemical reactivity of their organic substrates, enzymes performing biosynthetic and degradative halogenation chemistry utilize numerous mechanistic strategies involving oxidation, reduction, and substitution. Biosynthetic halogenation reactions range from simple aromatic substitutions to stereoselective C-H functionalizations on remote carbon centers and can initiate the formation of simple to complex ring structures. Dehalogenating enzymes, on the other hand, are best known for removing halogen atoms from man-made organohalogens, yet also function naturally, albeit rarely, in metabolic pathways. This review details the scope and mechanism of nature's halogenation and dehalogenation enzymatic strategies, highlights gaps in our understanding, and posits where new advances in the field might arise in the near future.