scholarly journals Comparison of the Anion Inhibition Profiles of the α-CA Isoforms (SpiCA1, SpiCA2 and SpiCA3) from the Scleractinian Coral Stylophora pistillata

2018 ◽  
Vol 19 (7) ◽  
pp. 2128 ◽  
Author(s):  
Sonia Del Prete ◽  
Silvia Bua ◽  
Didier Zoccola ◽  
Fatmah Alasmary ◽  
Zeid AlOthman ◽  
...  
Keyword(s):  
Small Molecules ◽  
Molecular Level ◽  
Carbonic Anhydrases ◽  
Efficient Catalyst ◽  
Stylophora Pistillata ◽  
Uncatalyzed Reaction ◽  
Physiological Processes ◽  
Cell Layers ◽  
Membrane Bound ◽  
Living Organisms

Carbonic anhydrases (CAs, EC 4.2.1.1) are widespread metalloenzymes used by living organisms to accelerate the CO2 hydration/dehydration reaction at rates dramatically high compared to the uncatalyzed reaction. These enzymes have different isoforms and homologues and can be found in the form of cytoplasmic, secreted or membrane-bound proteins. CAs play a role in numerous physiological processes including biomineralization and symbiosis, as is the case in reef-building corals. Previously, molecular and biochemical data have been obtained at the molecular level in the branching coral Stylophora pistillata for two coral isoforms which differ significantly in their catalytic activity and susceptibility to inhibition with anions and sulfonamides. More recently it has been determined that the genome of S. pistillata encodes for 16 CAs. Here, we cloned, expressed, purified and characterized a novel α-CA, named SpiCA3, which is cytoplasmic and ubiquitously expressed in all the cell layers including the calcifying cells. SpiCA3 is the most effective CA among the coral isoforms investigated and the most efficient catalyst known up to date in Metazoa. We also investigated the inhibition profiles of SpiCA3 and compared it with those obtained for the two other isoforms in the presence of inorganic anions and other small molecules known to interfere with metalloenzymes. These results suggest that S. pistillata has adapted its CA isoforms to achieve the physiological functions in different physicochemical microenvironments.

scholarly journals Differential localization of ion transporters suggests distinct cellular mechanisms for calcification and photosynthesis between two coral species

2015 ◽  
Vol 309 (3) ◽  
pp. R235-R246 ◽  
Author(s):  
Katie L. Barott ◽  
Sidney O. Perez ◽  
Lauren B. Linsmayer ◽  
Martin Tresguerres
Keyword(s):  
Ion Transport ◽  
Coral Species ◽  
Apical Membrane ◽  
Ph Regulation ◽  
Oral Epithelium ◽  
Ion Transporters ◽  
Cellular Mechanisms ◽  
Stylophora Pistillata ◽  
Physiological Processes ◽  
Cell Layers

Ion transport is fundamental for multiple physiological processes, including but not limited to pH regulation, calcification, and photosynthesis. Here, we investigated ion-transporting processes in tissues from the corals Acropora yongei and Stylophora pistillata, representatives of the complex and robust clades that diverged over 250 million years ago. Antibodies against complex IV revealed that mitochondria, an essential source of ATP for energetically costly ion transporters, were abundant throughout the tissues of A. yongei. Additionally, transmission electron microscopy revealed septate junctions in all cell layers of A. yongei, as previously reported for S. pistillata, as well as evidence for transcellular vesicular transport in calicoblastic cells. Antibodies against the alpha subunit of Na+/K+-ATPase (NKA) and plasma membrane Ca2+-ATPase (PMCA) immunolabeled cells in the calicoblastic epithelium of both species, suggesting conserved roles in calcification. However, NKA was abundant in the apical membrane of the oral epithelium in A. yongei but not S. pistillata, while PMCA was abundant in the gastroderm of S. pistillata but not A. yongei. These differences indicate that these two coral species utilize distinct pathways to deliver ions to the sites of calcification and photosynthesis. Finally, antibodies against mammalian sodium bicarbonate cotransporters (NBC; SLC4 family) resulted in strong immunostaining in the apical membrane of oral epithelial cells and in calicoblastic cells in A. yongei, a pattern identical to NKA. Characterization of ion transport mechanisms is an essential step toward understanding the cellular mechanisms of coral physiology and will help predict how different coral species respond to environmental stress.

scholarly journals Comparison of the Sulfonamide Inhibition Profiles of the α-Carbonic Anhydrase Isoforms (SpiCA1, SpiCA2 and SpiCA3) Encoded by the Genome of the Scleractinian Coral Stylophora pistillata

Marine Drugs ◽  
2019 ◽  
Vol 17 (3) ◽  
pp. 146 ◽  
Author(s):  
Sonia Del Prete ◽  
Silvia Bua ◽  
Fatmah Alasmary ◽  
Zeid AlOthman ◽  
Sylvie Tambutté ◽  
...  
Keyword(s):  
Plasma Membranes ◽  
Molecular Mechanisms ◽  
Ph Regulation ◽  
Protein Isoforms ◽  
Carbonic Anhydrases ◽  
Recombinant Enzymes ◽  
Stylophora Pistillata ◽  
Bicarbonate Transporters ◽  
Cell Layers ◽  
Inorganic Carbon Transport

The ubiquitous metalloenzymes carbonic anhydrases (CAs, EC 4.2.1.1) are responsible for the reversible hydration of CO2 to bicarbonate (HCO3−) and protons (H+). Bicarbonate may subsequently generate carbonate used in many functional activities by marine organisms. CAs play a crucial role in several physiological processes, e.g., respiration, inorganic carbon transport, intra and extra-cellular pH regulation, and bio-mineralization. Multiple transcript variants and protein isoforms exist in the organisms. Recently, 16 α-CA isoforms have been identified in the coral Stylophora pistillata. Here, we focalized the interest on three coral isoforms: SpiCA1 and SpiCA2, localized in the coral-calcifying cells; and SpiCA3, expressed in the cytoplasm of the coral cell layers. The three recombinant enzymes were heterologously expressed and investigated for their inhibition profiles with sulfonamides and sulfamates. The three coral CA isoforms differ significantly in their susceptibility to inhibition with sulfonamides. This study provides new insights into the coral physiology and the comprehension of molecular mechanisms involved in the bio-mineralization processes, since CAs interact with bicarbonate transporters, accelerating the trans-membrane bicarbonate movement and modulating the pH at both sides of the plasma membranes.

scholarly journals Alternative approaches to target Myc for cancer treatment

2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Chen Wang ◽  
Jiawei Zhang ◽  
Jie Yin ◽  
Yichao Gan ◽  
Senlin Xu ◽  
...  
Keyword(s):  
Cancer Treatment ◽  
Small Molecules ◽  
Drug Target ◽  
The Past ◽  
Physiological Processes ◽  
Alternative Approaches ◽  
Global Transcriptome ◽  
Factor C ◽  
Signaling Modules ◽  
Druggable Targets

AbstractThe Myc proto-oncogene family consists of three members, C-MYC, MYCN, and MYCL, which encodes the transcription factor c-Myc (hereafter Myc), N-Myc, and L-Myc, respectively. Myc protein orchestrates diverse physiological processes, including cell proliferation, differentiation, survival, and apoptosis. Myc modulates about 15% of the global transcriptome, and its deregulation rewires the cellular signaling modules inside tumor cells, thereby acquiring selective advantages. The deregulation of Myc occurs in >70% of human cancers, and is related to poor prognosis; hence, hyperactivated Myc oncoprotein has been proposed as an ideal drug target for decades. Nevertheless, no specific drug is currently available to directly target Myc, mainly because of its “undruggable” properties: lack of enzymatic pocket for conventional small molecules to bind; inaccessibility for antibody due to the predominant nucleus localization of Myc. Although the topic of targeting Myc has actively been reviewed in the past decades, exciting new progresses in this field keep emerging. In this review, after a comprehensive summarization of valuable sources for potential druggable targets of Myc-driven cancer, we also peer into the promising future of utilizing macropinocytosis to deliver peptides like Omomyc or antibody agents to intracellular compartment for cancer treatment.

scholarly journals Effect of Sulfonamides and Their Structurally Related Derivatives on the Activity of ι-Carbonic Anhydrase from Burkholderia territorii

2021 ◽  
Vol 22 (2) ◽  
pp. 571
Author(s):  
Viviana De Luca ◽  
Andrea Petreni ◽  
Alessio Nocentini ◽  
Andrea Scaloni ◽  
Claudiu T. Supuran ◽  
...  
Keyword(s):  
Carbon Dioxide ◽  
Antibiotic Resistance ◽  
Pathogenic Bacteria ◽  
Selective Inhibition ◽  
Extensive Study ◽  
Protein Isoforms ◽  
Carbonic Anhydrases ◽  
Physiological Processes ◽  
Microbial Survival ◽  
Reversible Hydration

Carbonic anhydrases (CAs) are essential metalloenzymes in nature, catalyzing the carbon dioxide reversible hydration into bicarbonate and proton. In humans, breathing and many other critical physiological processes depend on this enzymatic activity. The CA superfamily function and inhibition in pathogenic bacteria has recently been the object of significant advances, being demonstrated to affect microbial survival/virulence. Targeting bacterial CAs may thus be a valid alternative to expand the pharmacological arsenal against the emergence of widespread antibiotic resistance. Here, we report an extensive study on the inhibition profile of the recently discovered ι-CA class present in some bacteria, including Burkholderia territorii, namely BteCAι, using substituted benzene-sulfonamides and clinically licensed sulfonamide-, sulfamate- and sulfamide-type drugs. The BteCAι inhibition profile showed: (i) several benzene-sulfonamides with an inhibition constant lower than 100 nM; (ii) a different behavior with respect to other α, β and γ-CAs; (iii) clinically used drugs having a micromolar affinity. This prototype study contributes to the initial recognition of compounds which efficiently and selectively inhibit a bacterial member of the ι-CA class, for which such a selective inhibition with respect to other protein isoforms present in the host is highly desired and may contribute to the development of novel antimicrobials.

scholarly journals Functionalization Strategies of PEDOT and PEDOT:PSS Films for Organic Bioelectronics Applications

Chemosensors ◽  
2021 ◽  
Vol 9 (8) ◽  
pp. 212
Author(s):  
Gonzalo E. Fenoy ◽  
Omar Azzaroni ◽  
Wolfgang Knoll ◽  
Waldemar A. Marmisollé
Keyword(s):  
Small Molecules ◽  
Conducting Polymer ◽  
Organic Semiconductors ◽  
Synthesis Method ◽  
Polymer Synthesis ◽  
Preparation Methods ◽  
Electrophysiological Signals ◽  
Organic Bioelectronics ◽  
Biological Interfaces ◽  
Living Organisms

Organic bioelectronics involves the connection of organic semiconductors with living organisms, organs, tissues, cells, membranes, proteins, and even small molecules. In recent years, this field has received great interest due to the development of all kinds of devices architectures, enabling the detection of several relevant biomarkers, the stimulation and sensing of cells and tissues, and the recording of electrophysiological signals, among others. In this review, we discuss recent functionalization approaches for PEDOT and PEDOT:PSS films with the aim of integrating biomolecules for the fabrication of bioelectronics platforms. As the choice of the strategy is determined by the conducting polymer synthesis method, initially PEDOT and PEDOT:PSS films preparation methods are presented. Later, a wide variety of PEDOT functionalization approaches are discussed, together with bioconjugation techniques to develop efficient organic-biological interfaces. Finally, and by making use of these approaches, the fabrication of different platforms towards organic bioelectronics devices is reviewed.

scholarly journals CONCENTRATION AND PURIFICATION OF BACTERIOPHAGE

1938 ◽  
Vol 21 (3) ◽  
pp. 335-366 ◽  
Author(s):  
John H. Northrop
Keyword(s):  
Molecular Weight ◽  
Small Molecules ◽  
Specific Activity ◽  
Active Agent ◽  
Pure Substance ◽  
Solubility Curve ◽  
Denatured Protein ◽  
Sedimentation Constant ◽  
Rate Of Sedimentation ◽  
Living Organisms

1. A method for isolating a nucleoprotein from lysed staphylococci culture is described. 2. It is homogeneous in the ultracentrifuge and has a sedimentation constant of 650 x 10–13 cm. dyne–1 sec.–1, corresponding to a molecular weight of about 300,000,000. 3. The diffusion coefficient varies from about 0.001 cm.2/day in solutions containing more than 0.1 mg. protein/ml. to 0.02 in solutions containing less than 0.001 mg. protein/ml. The rate of sedimentation also decreases as the concentration decreases. It is suggested, therefore, that this protein exists in various sized molecules of from 500,000–300,000,000 molecular weight, the proportion of small molecules increasing as the concentration decreases. 4. This protein is very unstable and is denatured by acidity greater than pH 5.0, by temperature over 50°C. for 5 minutes. It is digested by chymo-trypsin but not by trypsin. 5. The loss in activity by heat, acid, and chymo-trypsin digestion is roughly proportional to the amount of denatured protein formed under these conditions. 6. The rate of diffusion of the protein is the same as that of the active agent. 7. The rate of sedimentation of the protein is the same as that of the active agent. 8. The loss in activity when susceptible living or dead bacteria are added to a solution of the protein is proportional to the loss in protein from the solution. Non-susceptible bacteria remove neither protein nor activity. 9. The relative ultraviolet light absorption, as determined directly, agrees with that calculated from Gates' inactivation experiments in the range of 2500–3000 Å. u. but is somewhat greater in the range of 2000–2500 Å. u. 10. Solubility determinations showed that most of the preparations contained at least two proteins, one being probably the denatured form of the other. Two preparations were obtained, however, which had about twice the specific activity of the earlier ones and which gave a solubility curve approximating that of a pure substance. 11. It is suggested that the formation of phage may be more simply explained by analogy with the autocatalytic formation of pepsin and trypsin than by analogy with the far more complicated system of living organisms.

scholarly journals Gamete-mediated mate choice: towards a more inclusive view of sexual selection

2018 ◽  
Vol 285 (1883) ◽  
pp. 20180836 ◽  
Author(s):  
Jukka Kekäläinen ◽  
Jonathan P. Evans
Keyword(s):  
Sexual Selection ◽  
Mate Choice ◽  
Sperm Competition ◽  
Female Choice ◽  
Mating Systems ◽  
Molecular Level ◽  
Evolutionary Significance ◽  
Random Interactions ◽  
Physiological Processes ◽  
The Everyday

‘Sperm competition’—where ejaculates from two or more males compete for fertilization—and ‘cryptic female choice’—where females bias this contest to suit their reproductive interests—are now part of the everyday lexicon of sexual selection. Yet the physiological processes that underlie these post-ejaculatory episodes of sexual selection remain largely enigmatic. In this review, we focus on a range of post-ejaculatory cellular- and molecular-level processes, known to be fundamental for fertilization across most (if not all) sexually reproducing species, and point to their putative role in facilitating sexual selection at the level of the cells and gametes, called ‘gamete-mediated mate choice’ (GMMC). In this way, we collate accumulated evidence for GMMC across different mating systems, and emphasize the evolutionary significance of such non-random interactions among gametes. Our overall aim in this review is to build a more inclusive view of sexual selection by showing that mate choice often acts in more nuanced ways than has traditionally been assumed. We also aim to bridge the conceptual divide between proximal mechanisms of reproduction, and adaptive explanations for patterns of non-random sperm–egg interactions that are emerging across an increasingly diverse array of taxa.

scholarly journals Self-reproducing catalyst drives repeated phospholipid synthesis and membrane growth

2015 ◽  
Vol 112 (27) ◽  
pp. 8187-8192 ◽  
Author(s):  
Michael D. Hardy ◽  
Jun Yang ◽  
Jangir Selimkhanov ◽  
Christian M. Cole ◽  
Lev S. Tsimring ◽  
...  
Keyword(s):  
Lipid Synthesis ◽  
Building Blocks ◽  
Phospholipid Bilayer ◽  
Phospholipid Synthesis ◽  
Synthetic Membranes ◽  
Design And Synthesis ◽  
Membrane Growth ◽  
Membrane Bound ◽  
Living Organisms ◽  
Dynamic Structures

Cell membranes are dynamic structures found in all living organisms. There have been numerous constructs that model phospholipid membranes. However, unlike natural membranes, these biomimetic systems cannot sustain growth owing to an inability to replenish phospholipid-synthesizing catalysts. Here we report on the design and synthesis of artificial membranes embedded with synthetic, self-reproducing catalysts capable of perpetuating phospholipid bilayer formation. Replacing the complex biochemical pathways used in nature with an autocatalyst that also drives lipid synthesis leads to the continual formation of triazole phospholipids and membrane-bound oligotriazole catalysts from simpler starting materials. In addition to continual phospholipid synthesis and vesicle growth, the synthetic membranes are capable of remodeling their physical composition in response to changes in the environment by preferentially incorporating specific precursors. These results demonstrate that complex membranes capable of indefinite self-synthesis can emerge when supplied with simpler chemical building blocks.

scholarly journals Development and Mining of a Volatile Organic Compound Database

2015 ◽  
Vol 2015 ◽  
pp. 1-13 ◽  
Author(s):  
Azian Azamimi Abdullah ◽  
Md. Altaf-Ul-Amin ◽  
Naoaki Ono ◽  
Tetsuo Sato ◽  
Tadao Sugiura ◽  
...  
Keyword(s):  
Small Molecules ◽  
Biological Activities ◽  
Biological Interactions ◽  
Ambient Conditions ◽  
Boiling Points ◽  
Volatile Organic ◽  
Care Field ◽  
High Vapor ◽  
Compound Database ◽  
Living Organisms

Volatile organic compounds (VOCs) are small molecules that exhibit high vapor pressure under ambient conditions and have low boiling points. Although VOCs contribute only a small proportion of the total metabolites produced by living organisms, they play an important role in chemical ecology specifically in the biological interactions between organisms and ecosystems. VOCs are also important in the health care field as they are presently used as a biomarker to detect various human diseases. Information on VOCs is scattered in the literature until now; however, there is still no available database describing VOCs and their biological activities. To attain this purpose, we have developed KNApSAcK Metabolite Ecology Database, which contains the information on the relationships between VOCs and their emitting organisms. The KNApSAcK Metabolite Ecology is also linked with the KNApSAcK Core and KNApSAcK Metabolite Activity Database to provide further information on the metabolites and their biological activities. The VOC database can be accessed online.

Fluorescence-Raman dual-mode quantitative detection and imaging of small-molecule thiols in cell apoptosis with DNA-modified gold nanoflowers

2022 ◽  
Author(s):  
Chenbiao Li ◽  
Peifang Chen ◽  
Imran Mahmood Khan ◽  
Zhouping Wang ◽  
Yin Zhang ◽  
...  
Keyword(s):  
Small Molecule ◽  
Cell Apoptosis ◽  
Quantitative Detection ◽  
Dual Mode ◽  
Physiological Processes ◽  
Gold Nanoflowers ◽  
Living Organisms

The monitoring of small-molecule thiols (especially glutathione) has attracted widespread attention due to their involvement in numerous physiological processes in living organisms and cells. In this work, the dual-mode nanosensor...

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