The ISWI family protein SMARCA5 contains the ATP-binding pocket that coordinates the catalytic Mg2+ ion and water molecules for ATP hydrolysis. In this study, we demonstrate that SMARCA5 can also possess an alternative metal-binding ability. First, we isolated SMARCA5 on the cobalt column (IMAC) to near homogeneity. Examination of the interactions of SMARCA5 with metal-chelating supports showed that, apart from Co2+, it binds to Cu2+, Zn2+ and Ni2+. The efficiency of the binding to the last-listed metal was influenced by the chelating ligand, resulting in a strong preference for Ni-NTA over the Ni-CM-Asp equivalent. To gain insight in the preferential affinity for the Ni-NTA ligand, QM calculations were performed on model systems and metal-ligand complexes with a limited protein fragment of SMARCA5 containing the double-histidine (dHis) motif. The calculations correlated the observed affinity with the relative stability of the d-block metals to tetradentate ligand coordination over tridentate, as well as their overall octahedral coordination capacity. Likewise, binding free energies derived from model imidazole complexes mirrored the observed Ni-NTA/Ni-CM-Asp preferential affinity. Finally, similar calculations on complexes with a SMARCA5 peptide fragment derived from the AlphaFold structural prediction, captured almost accurately the expected relative stability of the TM complexes, and produced a large energetic separation (~10 kcal∙mol-1) between Ni-NTA and Ni-CM-Asp in favour of the former.
- MeSH
- adenosintrifosfatasy MeSH
- chromozomální proteiny, nehistonové metabolismus chemie MeSH
- kovy chemie metabolismus MeSH
- kvantová teorie MeSH
- lidé MeSH
- ligandy MeSH
- molekulární modely MeSH
- restrukturace chromatinu MeSH
- vazba proteinů * MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
The bacterial secretome represents a comprehensive catalog of proteins released extracellularly that have multiple important roles in virulence and intercellular communication. This study aimed to characterize the secretome of an environmental isolate Pseudomonas aeruginosa S-8 by analyzing trypsin-digested culture supernatant proteins using nano-LC-MS/MS tool. Using a combined approach of bioinformatics and mass spectrometry, 1088 proteins in the secretome were analyzed by PREDLIPO, SecretomeP 2.0, SignalP 4.1, and PSORTb tool for their subcellular localization and further categorization of secretome proteins according to signal peptides. Using the gene ontology tool, secretome proteins were categorized into different functional categories. KEGG pathway analysis identified the secreted proteins into different metabolic functional pathways. Moreover, our LC-MS/MS data revealed the secretion of various CAZymes into the extracellular milieu, which suggests its strong biotechnological applications to breakdown complex carbohydrate polymers. The identified immunodominant epitopes from the secretome of P. aeruginosa showed the characteristic of being non-allergenic, highly antigenic, nontoxic, and having a low risk of triggering autoimmune responses, which highlights their potential as successful vaccine targets. Overall, the identification of secreted proteins of P. aeruginosa could be important for both diagnostic purposes and the development of an effective candidate vaccine.
- MeSH
- bakteriální proteiny * genetika metabolismus imunologie MeSH
- chromatografie kapalinová MeSH
- kovy metabolismus MeSH
- proteomika MeSH
- Pseudomonas aeruginosa * imunologie metabolismus genetika MeSH
- sekretom * metabolismus imunologie MeSH
- tandemová hmotnostní spektrometrie * MeSH
- výpočetní biologie * MeSH
- Publikační typ
- časopisecké články MeSH
Apart from oxygenic photosynthesis, the extent of manganese utilization in bacteria varies from species to species and also appears to depend on external conditions. This observation is in striking contrast to iron, which is similar to manganese but essential for the vast majority of bacteria. To adequately explain the role of manganese in pathogens, we first present in this review that the accumulation of molecular oxygen in the Earth's atmosphere was a key event that linked manganese utilization to iron utilization and put pressure on the use of manganese in general. We devote a large part of our contribution to explanation of how molecular oxygen interferes with iron so that it enhances oxidative stress in cells, and how bacteria have learned to control the concentration of free iron in the cytosol. The functioning of iron in the presence of molecular oxygen serves as a springboard for a fundamental understanding of why manganese is so valued by bacterial pathogens. The bulk of this review addresses how manganese can replace iron in enzymes. Redox-active enzymes must cope with the higher redox potential of manganese compared to iron. Therefore, specific manganese-dependent isoenzymes have evolved that either lower the redox potential of the bound metal or use a stronger oxidant. In contrast, redox-inactive enzymes can exchange the metal directly within the individual active site, so no isoenzymes are required. It appears that in the physiological context, only redox-inactive mononuclear or dinuclear enzymes are capable of replacing iron with manganese within the same active site. In both cases, cytosolic conditions play an important role in the selection of the metal used. In conclusion, we summarize both well-characterized and less-studied mechanisms of the tug-of-war for manganese between host and pathogen.
Metallothioneins (MTs) are small cysteine-rich intracellular proteins with four major isoforms identified in mammals, designated MT-1 through MT-4. The best known biological functions of MTs are their ability to bind and sequester metal ions as well as their active role in redox homeostasis. Despite these protective roles, numerous studies have demonstrated that changes in MT expression could be associated with the process of carcinogenesis and participation in cell differentiation, proliferation, migration, and angiogenesis. Hence, MTs have the role of double agents, i.e., working with and against cancer. In view of their rich biochemical properties, it is not surprising that MTs participate in the emergence of chemoresistance in tumor cells. Many studies have demonstrated that MT overexpression is involved in the acquisition of resistance to anticancer drugs including cisplatin, anthracyclines, tyrosine kinase inhibitors and mitomycin. The evidence is gradually increasing for a cellular switch in MT functions, showing that they indeed have two faces: protector and saboteur. Initially, MTs display anti-oncogenic and protective roles; however, once the oncogenic process was launched, MTs are utilized by cancer cells for progression, survival, and contribution to chemoresistance. The duality of MTs can serve as a potential prognostic/diagnostic biomarker and can therefore pave the way towards the development of new cancer treatment strategies. Herein, we review and discuss MTs as tumor disease markers and describe their role in chemoresistance to distinct anticancer drugs.
- MeSH
- chemorezistence genetika MeSH
- ionty metabolismus MeSH
- karcinogeneze genetika patologie MeSH
- kovy metabolismus MeSH
- lidé MeSH
- metalothionein genetika metabolismus MeSH
- nádorové biomarkery genetika metabolismus MeSH
- nádory diagnóza farmakoterapie genetika patologie MeSH
- prognóza MeSH
- progrese nemoci MeSH
- protein - isoformy genetika metabolismus MeSH
- protinádorové látky farmakologie terapeutické užití MeSH
- regulace genové exprese u nádorů MeSH
- staging nádorů MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
In-depth knowledge of cell metabolism and nutrient uptake mechanisms can lead to the development of a tool for improving acetone-butanol-ethanol (ABE) fermentation performance and help to overcome bottlenecks in the process, such as the high cost of substrates and low production rates. Over 300 genes potentially encoding transport of amino acids, metal ions, vitamins and carbohydrates were identified in the genome of the butanol-producing strain Clostridium beijerinckii NRRL B-598, based on similarity searches in protein function databases. Transcriptomic data of the genes were obtained during ABE fermentation by RNA-Seq experiments and covered acidogenesis, solventogenesis and sporulation. The physiological roles of the selected 81 actively expressed transport genes were established on the basis of their expression profiles at particular stages of ABE fermentation. This article describes how genes encoding the uptake of glucose, iron, riboflavin, glutamine, methionine and other nutrients take part in growth, production and stress responses of C. beijerinckii NRRL B-598. These data increase our knowledge of transport mechanisms in solventogenic Clostridium and may be used in the selection of individual genes for further research.
- MeSH
- aminokyseliny genetika metabolismus MeSH
- butanoly metabolismus MeSH
- Clostridium beijerinckii genetika metabolismus MeSH
- fermentace MeSH
- genetická transkripce * MeSH
- kovy metabolismus MeSH
- metabolismus sacharidů genetika MeSH
- regulace genové exprese u bakterií genetika MeSH
- sacharidy genetika MeSH
- vitaminy genetika metabolismus MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
The brain has a unique biological complexity and is responsible for important functions in the human body, such as the command of cognitive and motor functions. Disruptive disorders that affect this organ, e.g. neurodegenerative diseases (NDDs), can lead to permanent damage, impairing the patients' quality of life and even causing death. In spite of their clinical diversity, these NDDs share common characteristics, such as the accumulation of specific proteins in the cells, the compromise of the metal ion homeostasis in the brain, among others. Despite considerable advances in understanding the mechanisms of these diseases and advances in the development of treatments, these disorders remain uncured. Considering the diversity of mechanisms that act in NDDs, a wide range of compounds have been developed to act by different means. Thus, promising compounds with contrasting properties, such as chelating agents and metal-based drugs have been proposed to act on different molecular targets as well as to contribute to the same goal, which is the treatment of NDDs. This review seeks to discuss the different roles and recent developments of metal-based drugs, such as metal complexes and metal chelating agents as a proposal for the treatment of NDDs.
- MeSH
- amyloid chemie metabolismus MeSH
- amyloidní beta-protein chemie metabolismus MeSH
- chelátory chemie farmakologie terapeutické užití MeSH
- kovy chemie metabolismus MeSH
- lidé MeSH
- neurodegenerativní nemoci farmakoterapie etiologie metabolismus patologie MeSH
- přehodnocení terapeutických indikací léčivého přípravku MeSH
- simulace molekulární dynamiky MeSH
- simulace molekulového dockingu MeSH
- vyvíjení léků * MeSH
- vztahy mezi strukturou a aktivitou MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
We studied thallium (Tl) isotope fractionation in white mustard grown hydroponically at different Tl doses. Thallium isotope signatures in plants indicated preferential incorporation of the light 203Tl isotope during Tl uptake from the nutrient solution. Negative isotope fractionation was even more pronounced in dependence on how much the available Tl pool decreased. This finding corresponds to the concept of isotope overprinting related to a high contamination level in the growing media (solution or soil). Regarding Tl translocation in plants, we observed a large Tl isotope shift with an enrichment in the heavy 205Tl isotope in the shoots relative to the roots in treatments with low/moderate solution Tl concentrations (0.01/0.05 mg Tl/L), with the corresponding α205/203Tl fractionation factors of ˜1.007 and 1.003, respectively. This finding is probably a consequence of specific (plant) reactions of Tl replacing K in its cycle. The formation of the S-coordinated Tl(I) complexes, potentially affecting both Tl accumulation and Tl isotope fractionation in plants, however, was not proven in our plants, since we did not have indication for that on the basis of X-ray absorption spectroscopy, suggesting that Tl was mainly present as free/hydrated Tl+ ion or chemically bound to O-containing functional groups.
- MeSH
- algoritmy MeSH
- biomasa MeSH
- Brassica metabolismus MeSH
- hořčice rodu Brassica metabolismus MeSH
- kořeny rostlin metabolismus MeSH
- kovy metabolismus MeSH
- listy rostlin metabolismus MeSH
- radioaktivní znečišťující látky MeSH
- radioizotopy thallia chemie metabolismus MeSH
- stonky rostlin metabolismus MeSH
- thallium chemie metabolismus MeSH
- výhonky rostlin metabolismus MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Many trace metals are essential micronutrients, but also potent toxins. Due to natural and anthropogenic causes, vastly different trace metal concentrations occur in various habitats, ranging from deficient to toxic levels. Therefore, one focus of plant research is on the response to trace metals in terms of uptake, transport, sequestration, speciation, physiological use, deficiency, toxicity, and detoxification. In this review, we cover most of these aspects for the essential micronutrients copper, iron, manganese, molybdenum, nickel, and zinc to provide a broader overview than found in other recent reviews, to cross-link aspects of knowledge in this very active research field that are often seen in a separated way. For example, individual processes of metal usage, deficiency, or toxicity often were not mechanistically interconnected. Therefore, this review also aims to stimulate the communication of researchers following different approaches, such as gene expression analysis, biochemistry, or biophysics of metalloproteins. Furthermore, we highlight recent insights, emphasizing data obtained under physiologically and environmentally relevant conditions.
- MeSH
- kovy metabolismus MeSH
- rostliny metabolismus MeSH
- stopové prvky metabolismus MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
The experiment was carried out in order to evaluate the effects of trace element immobilizing soil amendments, i.e., chalcedonite, dolomite, halloysite, and diatomite on the chemical characteristics of soil contaminated with Cr and the uptake of metals by plants. The study utilized analysis of variance (ANOVA), principal component analysis (PCA) and Factor Analysis (FA). The content of trace elements in plants, pseudo-total and extracted by 0.01 M CaCl₂, were determined using the method of spectrophotometry. All of the investigated element contents in the tested parts of Indian mustard (Brassica juncea L.) differed significantly in the case of applying amendments to the soil, as well as Cr contamination. The greatest average above-ground biomass was observed when halloysite and dolomite were amended to the soil. Halloysite caused significant increases of Cr concentrations in the roots. The obtained values of bioconcentration and translocation factors observed for halloysite treatment indicate the effectiveness of using Indian mustard in phytostabilization techniques. The addition of diatomite significantly increased soil pH. Halloysite and chalcedonite were shown to be the most effective and decreased the average Cr, Cu and Zn contents in soil.
- MeSH
- biodegradace MeSH
- biomasa MeSH
- hořčice rodu Brassica metabolismus MeSH
- hořčík chemie MeSH
- jíl MeSH
- koncentrace vodíkových iontů MeSH
- kořeny rostlin metabolismus MeSH
- kovy chemie metabolismus MeSH
- látky znečišťující půdu chemie metabolismus MeSH
- oxid křemičitý chemie MeSH
- průmysl MeSH
- průmyslový odpad MeSH
- půda chemie MeSH
- silikáty hliníku chemie MeSH
- uhličitan vápenatý chemie MeSH
- Publikační typ
- časopisecké články MeSH
Nanomaterials in agriculture are becoming popular due to the impressive advantages of these particles. However, their bioavailability and toxicity are key features for their massive employment. Herein, we comprehensively summarize the latest findings on the phytotoxicity of nanomaterial products based on essential metals used in plant protection. The metal nanoparticles (NPs) synthesized from essential metals belong to the most commonly manufactured types of nanomaterials since they have unique physical and chemical properties and are used in agricultural and biotechnological applications, which are discussed. The paper discusses the interactions of nanomaterials and vascular plants, which are the subject of intensive research because plants closely interact with soil, water, and atmosphere; they are also part of the food chain. Regarding the accumulation of NPs in the plant body, their quantification and localization is still very unclear and further research in this area is necessary.
