scholarly journals Novel Interactions of Adrenodoxin-Related [2Fe-2S] Plant Ferredoxins MFDX1 and MFDX2 Indicate Their Involvement in a Wide Spectrum of Functions in Plant Mitochondria

2019 ◽  
Vol 73 (6) ◽  
pp. 478-486
Author(s):  
Elena K. Shematorova ◽  
Ivan Yu. Slovokhotov ◽  
Vladimir N. Shmakov ◽  
Marat R. Khaliluev ◽  
Dmitry G. Shpakovski ◽  
...  
Keyword(s):  
Protein Complexes ◽  
Wide Spectrum ◽  
Plant Mitochondria ◽  
Mitochondrial Protein ◽  
Regulatory System ◽  
Structural Features ◽  
Cytochrome P450scc ◽  
Digitalis Purpurea ◽  
Wide Range ◽  
Range Of Functions

Abstract Electron transfer chains of plant organelles (both chloroplasts and mitochondria) contain their own special set of ferredoxins. The relatively recently described adrenodoxin-like [2Fe-2S]-ferredoxins MFDX1 and MFDX2 of plant mitochondria are among the least studied of these. Until now, the only established function for them is participation in the final stage of biotin biosynthesis. In this work, using genetic and biochemical approaches, we searched for possible partners of these proteins in the genomes and proteomes of tobacco (Nicotiana tabacum L.) and foxglove (Digitalis purpurea L.) plants. MORF9 protein, one of the auxiliary components of the RNA editing complex of organelles (editosome), was found among the most prominent protein partners of adrenodoxin-like [2Fe-2S] tobacco ferredoxins. According to the results obtained from the yeast two-hybrid system, NtMFDX1 and NtMFDX2 of tobacco also bind and interact productively with the previously uncharacterised long non-coding polyadenylated RNA, which, based on its structural features, is capable of regulating the function of a number of components of complexes I (Nad1, Nad5) and III (protein of the cytochrome c synthesis system CcmF) and contributes to the formation of Fe/S-clusters in the corresponding protein complexes of the respiratory chain of plant mitochondria. We found one of the main components of the thiazol synthase complex (mitochondrial protein DpTHI1) to be the partner of ferredoxin DpMFDX2 of Digitalis purpurea. Finally, additional arguments were obtained in favour of the possible participation of MFDX1 and MFDX2 in the very ancient, but only recently described ‘progesterone’ steroid hormonal regulatory system: in leaves of the previously constructed CYP11A1-transgenic tomato plants, only the mature form of mitochondrial cytochrome P450scc (CYP11A1) of mammals is able to enter the mitochondria, where the above-mentioned components of the electron transport chain are localised. In summary, all of the newly revealed interactions of adrenodoxin-like [2Fe-2S] ferredoxins MFDX1 and MFDX2 indicate their participation in a wide range of functions in plant mitochondria.

scholarly journals Maize pentatricopeptide repeat protein DEK53 is required for mitochondrial RNA editing at multiple sites and seed development

2020 ◽  
Vol 71 (20) ◽  
pp. 6246-6261 ◽  
Author(s):  
Dawei Dai ◽  
Lifang Jin ◽  
Zhenzhen Huo ◽  
Shumei Yan ◽  
Zeyang Ma ◽  
...  
Keyword(s):  
Rna Editing ◽  
Protein Complexes ◽  
Plant Mitochondria ◽  
Mitochondrial Protein ◽  
Electron Microscopic Examination ◽  
Complex Iii ◽  
Mitochondrial Rna ◽  
Pentatricopeptide Repeat ◽  
Electron Microscopic ◽  
Ppr Protein

Abstract Pentatricopeptide repeat (PPR) proteins were identified as site-specific recognition factors for RNA editing in plant mitochondria and plastids. In this study, we characterized maize (Zea mays) kernel mutant defective kernel 53 (dek53), which has an embryo lethal and collapsed endosperm phenotype. Dek53 encodes an E-subgroup PPR protein, which possesses a short PLS repeat region of only seven repeats. Subcellular localization analysis indicated that DEK53 is localized in the mitochondrion. Strand- and transcript-specific RNA-seq analysis showed that the dek53 mutation affected C-to-U RNA editing at more than 60 mitochondrial C targets. Biochemical analysis of mitochondrial protein complexes revealed a significant reduction in the assembly of mitochondrial complex III in dek53. Transmission electron microscopic examination showed severe morphological defects of mitochondria in dek53 endosperm cells. In addition, yeast two-hybrid and luciferase complementation imaging assays indicated that DEK53 can interact with the mitochondrion-targeted non-PPR RNA editing factor ZmMORF1, suggesting that DEK53 might be a functional component of the organellar RNA editosome.

Beyond dsRNA: Toll-like receptor 3 signalling in RNA-induced immune responses

2014 ◽  
Vol 458 (2) ◽  
pp. 195-201 ◽  
Author(s):  
Megumi Tatematsu ◽  
Tsukasa Seya ◽  
Misako Matsumoto
Keyword(s):  
Immune Responses ◽  
Transmembrane Protein ◽  
Wide Spectrum ◽  
Physiological Role ◽  
Structural Features ◽  
Dendritic Cell Maturation ◽  
Type I ◽  
Toll Like Receptor ◽  
Wide Range ◽  
Infection And Inflammation

The innate immune system recognizes pathogen- and damage-associated molecular patterns using pattern-recognition receptors that activate a wide range of signalling cascades to maintain host homoeostasis against infection and inflammation. Endosomal TLR3 (Toll-like receptor 3), a type I transmembrane protein, senses RNAs derived from cells with viral infection or sterile tissue damage, leading to the induction of type I interferon and cytokine production, as well as dendritic cell maturation. It has been accepted that TLR3 recognizes perfect dsRNA, but little has been addressed experimentally with regard to the structural features of virus- or host-derived RNAs that activate TLR3. Recently, a TLR3 agonist was identified, which was a virus-derived ‘structured’ RNA with incomplete stem structures. Both dsRNA and structured RNA are similarly internalized through clathrin- and raftlin-dependent endocytosis and delivered to endosomal TLR3. The dsRNA uptake machinery, in addition to TLR3, is critical for extracellular viral RNA-induced immune responses. A wide spectrum of TLR3 ligand structures beyond dsRNA and their delivery systems provide new insights into the physiological role of TLR3 in virus- or host-derived RNA-induced immune responses. In the present paper, we focus on the system for extracellular recognition of RNA and its delivery to TLR3.

scholarly journals (Hydr)oxo-bridged heme complexes: From structure to reactivity

2019 ◽  
Vol 23 (11n12) ◽  
pp. 1286-1307
Author(s):  
Maria C. Carrasco ◽  
Shabnam Hematian
Keyword(s):  
Functional Materials ◽  
Structural Features ◽  
Nitric Oxide Reductase ◽  
Iron Porphyrins ◽  
Heme Enzymes ◽  
Coordination Environment ◽  
Wide Range ◽  
Comprehensive Picture ◽  
Range Of Functions ◽  
Copper Oxidase

Iron–porphyrins ([Formula: see text] hemes) are present throughout the biosphere and perform a wide range of functions, particularly those that involve complex multiple-electron redox processes. Some common heme enzymes involved in these processes include cytochrome P450, heme/copper oxidase or heme/non-heme diiron nitric oxide reductase. Consequently, the (hydr)oxo-bridged heme species have been studied for the important roles that they play in many life processes or for their application for catalysis and preparation of new functional materials. This review encompasses important synthetic, structural and reactivity aspects of the (hydr)oxo-bridged heme constructs that govern their function and application. The properties and reactivity of the bridging (hydr)oxo moieties are directly dictated by the coordination environment of the heme core, the nature and ligation of the second metal center attached to the (hydr)oxo group, the presence or absence of a linker, and the degree of flexibility around that linker within the scaffold. Here, we summarize the structural features of all known (hydr)oxo-bridged heme constructs and use those to categorize and thus, provide a more comprehensive picture of structure–function relationships.

Chaperonin as the normal controls and pathological anti-stress response in the human reproductive system

2016 ◽  
pp. 126-129
Author(s):  
M. Makarenko ◽  
◽  
D. Hovsyeyev ◽  
L. Sydoryk ◽  
◽  
...  
Keyword(s):  
Reproductive System ◽  
Stress Proteins ◽  
Physiological Stress ◽  
Protein Complexes ◽  
Reproductive Function ◽  
Intercellular Signaling ◽  
Toll Like Receptors ◽  
Wide Range ◽  
Protein Functions ◽  
And Function

Different kinds of physiological stress cause mass changes in the cells, including the changes in the structure and function of the protein complexes and in separate molecules. The protein functions is determined by its folding (the spatial conclusion), which depends on the functioning of proteins of thermal shock- molecular chaperons (HSPs) or depends on the stress proteins, that are high-conservative; specialized proteins that are responsible for the correct proteinaceous folding. The family of the molecular chaperones/ chaperonins/ Hsp60 has a special place due to the its unique properties of activating the signaling cascades through the system of Toll-like receptors; it also stimulates the cells to produce anti- inflammatory cytokines, defensins, molecules of cell adhesion and the molecules of MHC; it functions as the intercellular signaling molecule. The pathological role of Hsp60 is established in a wide range of illnesses, from diabetes to atherosclerosis, where Hsp60 takes part in the regulation of both apoptosis and the autoimmune processes. The presence of the HSPs was found in different tissues that are related to the reproductive system. Key words: molecular chaperons (HSPs), Toll-like receptors, reproductive function, natural auto antibody.

Rapid Online Buffer Exchange: A Method for Screening of Proteins, Protein Complexes, and Cell Lysates by Native Mass Spectrometry

2019 ◽  
Author(s):  
Zachary VanAernum ◽  
Florian Busch ◽  
Benjamin J. Jones ◽  
Mengxuan Jia ◽  
Zibo Chen ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
High Speed ◽  
Structural Information ◽  
Protein Complexes ◽  
High Sensitivity ◽  
Native Mass Spectrometry ◽  
Structural Features ◽  
Consumer Products ◽  
Cell Lysates ◽  
Protein Expression And Purification

It is important to assess the identity and purity of proteins and protein complexes during and after protein purification to ensure that samples are of sufficient quality for further biochemical and structural characterization, as well as for use in consumer products, chemical processes, and therapeutics. Native mass spectrometry (nMS) has become an important tool in protein analysis due to its ability to retain non-covalent interactions during measurements, making it possible to obtain protein structural information with high sensitivity and at high speed. Interferences from the presence of non-volatiles are typically alleviated by offline buffer exchange, which is timeconsuming and difficult to automate. We provide a protocol for rapid online buffer exchange (OBE) nMS to directly screen structural features of pre-purified proteins, protein complexes, or clarified cell lysates. Information obtained by OBE nMS can be used for fast (<5 min) quality control and can further guide protein expression and purification optimization.

pH-Dependent Thermal Stability of Vibrio cholerae L-asparaginase

2019 ◽  
Vol 26 (10) ◽  
pp. 743-750 ◽  
Author(s):  
Remya Radha ◽  
Sathyanarayana N. Gummadi
Keyword(s):  
Vibrio Cholerae ◽  
Conformational Changes ◽  
Kinetic Studies ◽  
Structural Features ◽  
Structure Stability ◽  
Kcal Mole ◽  
Scanning Calorimetry ◽  
Wide Range ◽  
Ph Dependent ◽  
Ph Range

Background:pH is one of the decisive macromolecular properties of proteins that significantly affects enzyme structure, stability and reaction rate. Change in pH may protonate or deprotonate the side group of aminoacid residues in the protein, thereby resulting in changes in chemical and structural features. Hence studies on the kinetics of enzyme deactivation by pH are important for assessing the bio-functionality of industrial enzymes. L-asparaginase is one such important enzyme that has potent applications in cancer therapy and food industry.Objective:The objective of the study is to understand and analyze the influence of pH on deactivation and stability of Vibrio cholerae L-asparaginase.Methods:Kinetic studies were conducted to analyze the effect of pH on stability and deactivation of Vibrio cholerae L-asparaginase. Circular Dichroism (CD) and Differential Scanning Calorimetry (DSC) studies have been carried out to understand the pH-dependent conformational changes in the secondary structure of V. cholerae L-asparaginase.Results:The enzyme was found to be least stable at extreme acidic conditions (pH< 4.5) and exhibited a gradual increase in melting temperature from 40 to 81 °C within pH range of 4.0 to 7.0. Thermodynamic properties of protein were estimated and at pH 7.0 the protein exhibited ΔG37of 26.31 kcal mole-1, ΔH of 204.27 kcal mole-1 and ΔS of 574.06 cal mole-1 K-1.Conclusion:The stability and thermodynamic analysis revealed that V. cholerae L-asparaginase was highly stable over a wide range of pH, with the highest stability in the pH range of 5.0–7.0.

Protein Interaction Domains and Post-Translational Modifications: Structural Features and Drug Discovery Applications

2020 ◽  
Vol 27 (37) ◽  
pp. 6306-6355 ◽  
Author(s):  
Marian Vincenzi ◽  
Flavia Anna Mercurio ◽  
Marilisa Leone
Keyword(s):  
Drug Discovery ◽  
Protein Interaction ◽  
Protein Interactions ◽  
Structural Information ◽  
Protein Complexes ◽  
Structural Features ◽  
Protein Protein Interactions ◽  
Modular Architecture ◽  
Post Translational Modifications ◽  
Interaction Domains

Background:: Many pathways regarding healthy cells and/or linked to diseases onset and progression depend on large assemblies including multi-protein complexes. Protein-protein interactions may occur through a vast array of modules known as protein interaction domains (PIDs). Objective:: This review concerns with PIDs recognizing post-translationally modified peptide sequences and intends to provide the scientific community with state of art knowledge on their 3D structures, binding topologies and potential applications in the drug discovery field. Method:: Several databases, such as the Pfam (Protein family), the SMART (Simple Modular Architecture Research Tool) and the PDB (Protein Data Bank), were searched to look for different domain families and gain structural information on protein complexes in which particular PIDs are involved. Recent literature on PIDs and related drug discovery campaigns was retrieved through Pubmed and analyzed. Results and Conclusion:: PIDs are rather versatile as concerning their binding preferences. Many of them recognize specifically only determined amino acid stretches with post-translational modifications, a few others are able to interact with several post-translationally modified sequences or with unmodified ones. Many PIDs can be linked to different diseases including cancer. The tremendous amount of available structural data led to the structure-based design of several molecules targeting protein-protein interactions mediated by PIDs, including peptides, peptidomimetics and small compounds. More studies are needed to fully role out, among different families, PIDs that can be considered reliable therapeutic targets, however, attacking PIDs rather than catalytic domains of a particular protein may represent a route to obtain selective inhibitors.

Cucurbitacins as Anticancer Agents: A Patent Review

2019 ◽  
Vol 14 (2) ◽  
pp. 133-143 ◽  
Author(s):  
Hidayat Hussain ◽  
Ivan R. Green ◽  
Muhammad Saleem ◽  
Khanzadi F. Khattak ◽  
Muhammad Irshad ◽  
...  
Keyword(s):  
Anticancer Agents ◽  
Wide Spectrum ◽  
Biological Effects ◽  
Therapeutic Effects ◽  
Cytotoxic Effects ◽  
Natural Sources ◽  
Oh Groups ◽  
Drug Candidates ◽  
The Past ◽  
Wide Range

Background: Cucurbitacins belong to a group of tetracyclic triterpenoids that display a wide range of biological effects. In the past, numerous cucurbitacins have been isolated from natural sources and many active compounds have been synthesized using the privileged scaffold in order to enhance its cytotoxic effects. Objective: his review covers patents on the therapeutic effects of natural cucurbitacins and their synthetic analogs published during the past decade. By far, the majority of patents published are related to cancer and Structure-Activity Relationships (SAR) of these compounds are included to lend gravitas to this important class of natural products. Methods: The date about the published patents was downloaded via online open access patent databases. Results: Cucurbitacins display significant cytotoxic properties, in particular cucurbitacins B and D which possess very potent effects towards a number of cancer cells. Numerous cucurbitacins isolated from natural sources have been derivatized through chemical modification at the C(2)-OH and C(25)- OH groups. Most importantly, an acyl ester of the C(25)-OH and, iso-propyl, n-propyl and ethyl ether groups of the C(2)-OH demonstrated the most increased cytotoxic activity. Conclusion: The significant cytotoxic effects of natural and semi-synthetic cucurbitacins make them attractive as new drug candidates. Moreover, cucurbitacins have the capability to form conjugates with other anticancer drugs which will synergistically enhance their anticancer effects. The authors believe that in order to get lead compounds, there should be a greater focus on the synthesis of homodimers, heterodimers, and halo derivatives of cucurbitacins. In the opinion of the authors the analysis of the published patents on the cucurbitacins indicates that these compounds can be developed into a regimen to treat a wide spectrum of cancers.

Structure, Function and Interactions of Tau: Particular Focus on Potential Drug Targets for the Treatment of Tauopathies

2018 ◽  
Vol 17 (5) ◽  
pp. 325-337 ◽  
Author(s):  
Hojjat Borna ◽  
Kasim Assadoulahei ◽  
Gholamhossein Riazi ◽  
Asghar Beigi Harchegani ◽  
Alireza Shahriary
Keyword(s):  
Tau Protein ◽  
Drug Targets ◽  
Brain Injuries ◽  
Potential Drug ◽  
Microtubule Network ◽  
Wide Range ◽  
Potential Risk Factors ◽  
Range Of Functions ◽  
Potential Drug Targets

Background & Objective: Neurodegenrative diseases are among the most widespread lifethreatening disorders around the world in elderly ages. The common feature of a group of neurodegenerative disorders, called tauopathies, is an accumulation of microtubule associated protein tau inside the neurons. The exact mechanism underlying tauopathies is not well-understood but several factors such as traumatic brain injuries and genetics are considered as potential risk factors. Although tau protein is well-known for its key role in stabilizing and organization of axonal microtubule network, it bears a broad range of functions including DNA protection and participation in signaling pathways. Moreover, the flexible unfolded structure of tau facilitates modification of tau by a wide range of intracellular enzymes which in turn broadens tau function and interaction spectrum. The distinctive properties of tau protein concomitant with the crucial role of tau interaction partners in the progression of neurodegeneration suggest tau and its binding partners as potential drug targets for the treatment of neurodegenerative diseases. Conclusion: This review aims to give a detailed description of structure, functions and interactions of tau protein in order to provide insight into potential therapeutic targets for treatment of tauopathies.

Application of Nitrogen Heterocyclic Carbenes in Organocatalysis

2020 ◽  
Vol 09 ◽  
Author(s):  
Minita Ojha ◽  
R. K. Bansal
Keyword(s):  
Asymmetric Catalysis ◽  
Building Blocks ◽  
Structural Features ◽  
Heterocyclic Carbenes ◽  
Stetter Reaction ◽  
Metal Pollutants ◽  
Synthetic Strategy ◽  
Wide Range ◽  
Benzoin Condensation ◽  
Nitrogen Heterocyclic

Background: During the last two decades, horizon of research in the field of Nitrogen Heterocyclic Carbenes (NHC) has widened remarkably. NHCs have emerged as ubiquitous species having applications in a broad range of fields, including organocatalysis and organometallic chemistry. The NHC-induced non-asymmetric catalysis has turned out to be a really fruitful area of research in recent years. Methods: By manipulating structural features and selecting appropriate substituent groups, it has been possible to control the kinetic and thermodynamic stability of a wide range of NHCs, which can be tolerant to a variety of functional groups and can be used under mild conditions. NHCs are produced by different methods, such as deprotonation of Nalkylhetrocyclic salt, transmetallation, decarboxylation and electrochemical reduction. Results: The NHCs have been used successfully as catalysts for a wide range of reactions making a large number of building blocks and other useful compounds accessible. Some of these reactions are: benzoin condensation, Stetter reaction, Michael reaction, esterification, activation of esters, activation of isocyanides, polymerization, different cycloaddition reactions, isomerization, etc. The present review includes all these examples published during the last 10 years, i.e. from 2010 till date. Conclusion: The NHCs have emerged as versatile and powerful organocatalysts in synthetic organic chemistry. They provide the synthetic strategy which does not burden the environment with metal pollutants and thus fit in the Green Chemistry.

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