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1.
Adv Exp Med Biol ; 1148: 1-24, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31482492

RESUMO

The use of therapeutic enzymes embraces currently a vast array of applications, abridging from diggestive disorders to cancer therapy, cardiovascular and lysosomal storage diseases. Enzyme drugs bind and act on their targets with great affinity and specificity, converting substrates to desired products in a reduced time frame with minimal side reactions. These characteristics have resulted in the development of a multitude of enzyme biopharmaceuticals for a wide range of human disorders.The advances in genetic engineering and DNA recombination techniques facilitated the production of therapeutical human-like enzymes, using different cells as host organisms. The selection of hosts generally privileges those that secrete the enzyme into the culture medium, as this eases the purification process, and those that are able to express complex glycoproteins, with glycosylation patterns and other post-translational modifications close to human proteins. Moreover, engineering approaches such as pegylation, encapsulation in micro- and nanocarriers, and mutation of amino acid residues of the native enzyme molecule to yield variants with improved therapeutic activity, half-life and/or stability, have been also addressed. Engineered enzyme products have been designed to display enhanced delivery to target sites and reduced adverse side-effects (e.g., immunogenicity) upon continuous drug administration.Irrespectively of the production method, the final formulation of therapeutic enzymes must display high purity and specificity, and they are often marketed as lyophilized pure preparations with biocompatible buffering salts and diluents to prepare the reconstituted aqueous solution before treatment.


Assuntos
Enzimas/biossíntese , Enzimas/isolamento & purificação , Enzimas/farmacologia , Produtos Biológicos , Meios de Cultura , Engenharia Genética , Glicosilação , Humanos , Processamento de Proteína Pós-Traducional , Proteínas Recombinantes
2.
Gene ; 718: 144049, 2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31430520

RESUMO

The role of epigenetics in development has garnered attention in recent years due to their ability to modulate the embryonic developmental gene expression in response to the environmental cues. The epigenetic mechanisms - DNA methylation, histone modification, and non-coding RNAs have a unique impact on vertebrate development. Zebrafish, a model vertebrate organism is being used widely in developmental studies due to their high fecundability and rapid organogenesis. With increased studies on various aspects of epigenetics in development, this review gives a glimpse of the major epigenetic modifications and their role in zebrafish development. In this review, the basic mechanism behind each modification followed by their status in zebrafish has been reviewed. Further, recent advancements in the epigenetic aspect of zebrafish development have been discussed.


Assuntos
Metilação de DNA/fisiologia , Embrião não Mamífero/embriologia , Desenvolvimento Embrionário/fisiologia , Epigênese Genética/fisiologia , Regulação da Expressão Gênica no Desenvolvimento/fisiologia , Peixe-Zebra/embriologia , Animais , Histonas/genética , Histonas/metabolismo , Processamento de Proteína Pós-Traducional/fisiologia , Peixe-Zebra/genética
3.
Adv Exp Med Biol ; 1158: 59-70, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31452135

RESUMO

Mitochondria have a central role in cellular metabolism and reversible post-translational modifications regulate activity of mitochondrial proteins. Thanks to advances in proteomics, lysine acetylation has arisen as an important post-translational modification in the mitochondrion. During acetylation an acetyl group is covalently attached to the epsilon amino group in the side chain of lysine residues using acetyl-CoA as the substrate donor. Therefore the positive charge is neutralized, and this can affect the function of proteins thereby regulating enzyme activity, protein interactions, and protein stability. The major deacetylase in mitochondria is SIRT3 whose activity regulates many mitochondrial enzymes. The method of choice for the analysis of acetylated proteins foresees the combination of mass spectrometry-based proteomics with affinity enrichment techniques. Beyond the identification of lysine-acetylated proteins, many studies are moving towards the characterization of acetylated patterns in different diseases. Indeed, modifications in lysine acetylation status can directly alter mitochondrial function and, therefore, be linked to human diseases such as metabolic diseases, cancer, myocardial injury and neurodegenerative diseases. Despite the progress in the characterization of different lysine acetylation sites, additional studies are needed to differentiate the specific changes with a significant biological relevance.


Assuntos
Lisina , Mitocôndrias , Fenótipo , Acetilação , Humanos , Lisina/metabolismo , Mitocôndrias/química , Mitocôndrias/metabolismo , Proteínas Mitocondriais/química , Proteínas Mitocondriais/metabolismo , Processamento de Proteína Pós-Traducional
4.
Results Probl Cell Differ ; 67: 17-25, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31435790

RESUMO

Acetylation is among the most prevalent posttranslational modifications in cells and regulates a number of physiological processes such as gene transcription, cell metabolism, and cell signaling. Although initially discovered on nuclear histones, many non-nuclear proteins have subsequently been found to be acetylated as well. The centrosome is the major microtubule-organizing center in most metazoans. Recent proteomic data indicate that a number of proteins in this subcellular compartment are acetylated. This review gives an overview of our current knowledge on protein acetylation at the centrosome and its functional relevance in organelle biology.


Assuntos
Centrossomo/metabolismo , Processamento de Proteína Pós-Traducional , Proteínas/metabolismo , Acetilação , Animais , Histonas/metabolismo , Humanos , Proteômica
5.
Biomed Khim ; 65(4): 263-276, 2019 Jun.
Artigo em Russo | MEDLINE | ID: mdl-31436168

RESUMO

Protein p53 is one of the most studied proteins. This attention is primarily due to its key role in the cellular mechanisms associated with carcinogenesis. Protein p53 is a transcription factor involved in a wide variety of processes: cell cycle regulation and apoptosis, signaling inside the cell, DNA repair, coordination of metabolic processes, regulation of cell interactions, etc. This multifunctionality is apparently determined by the fact that p53 is a vivid example of how the same protein can be represented by numerous proteoforms bearing completely different functional loads. By alternative splicing, using different promoters and translation initiation sites, the TP53 gene gives rise to at least 12 isoforms, which can additionally undergo numerous (>200) post-translational modifications. Proteoforms generated due to numerous point mutations in the TP53 gene are adding more complexity to this picture. The proteoforms produced are involved in various processes, such as the regulation of p53 transcriptional activity in response to various factors. This review is devoted to the description of the currently known p53 proteoforms, as well as their possible functionality.


Assuntos
Processamento Alternativo , Genes p53 , Proteína Supressora de Tumor p53/química , Humanos , Mutação Puntual , Isoformas de Proteínas/química , Processamento de Proteína Pós-Traducional , Relação Estrutura-Atividade
6.
Life Sci ; 234: 116768, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31445027

RESUMO

In prostate cancer development, the androgen receptor (AR) signaling plays a crucial role during both formation of early prostate lesions and progression to the lethal, incurable castration resistant stage. Accordingly, numerous approaches have been developed to inhibit AR activity including androgen deprivation therapy, application of the AR antagonists as well as the use of taxanes. However, these treatments, although effective initially, resistance inevitably occur for most of the patients within several years and limiting the therapeutic efficacy. Of note, alterations and reactivation of the AR signaling pathway have been demonstrated as the major reasons for the observed resistance. Accumulating evidences have suggested that synthesis of AR splicing variants, in particular, the constitutively active AR-V7, is one of the most important mechanisms that contribute to the abnormal AR signaling. In addition, clinical data also highlight the potential of using AR-V7 as a predictive biomarker and a therapeutic target in metastatic castration resistant prostate cancer (mCRPC). In this review, we summarize the recent findings concerning the specific role of AR-V7 in CRPC progression, drug resistance and its potential value in clinical assessment.


Assuntos
Antagonistas de Receptores de Andrógenos/uso terapêutico , Antineoplásicos/uso terapêutico , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Neoplasias de Próstata Resistentes à Castração/genética , Receptores Androgênicos/genética , Taxoides/uso terapêutico , Antagonistas de Receptores de Andrógenos/farmacologia , Animais , Antineoplásicos/farmacologia , Progressão da Doença , Resistencia a Medicamentos Antineoplásicos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Masculino , Neoplasias de Próstata Resistentes à Castração/metabolismo , Neoplasias de Próstata Resistentes à Castração/patologia , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , Processamento de Proteína Pós-Traducional/efeitos dos fármacos , Receptores Androgênicos/metabolismo , Transdução de Sinais/efeitos dos fármacos , Taxoides/farmacologia
7.
Adv Exp Med Biol ; 1140: 1-26, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31347039

RESUMO

Within the past years, we have witnessed a great improvement is mass spectrometry (MS) and proteomics approaches in terms of instrumentation, protein fractionation, and bioinformatics. With the current technology, protein identification alone is no longer sufficient. Both scientists and clinicians want not only to identify the proteins, but also to identify the protein's post-translational modifications (PTMs), protein isoforms, protein truncation, protein-protein interactions (PPI), and protein quantitation. Here, we describe the principle of MS and proteomics, and strategies to identify proteins, protein's PTMs, protein isoforms, protein truncation, PPIs, and protein quantitation. We also discuss the strengths and weaknesses within this field. Finally, in our concluding remarks we assess the role of mass spectrometry and proteomics in the scientific and clinical settings, in the near future. This chapter provides an introduction and overview for subsequent chapters that will discuss specific MS proteomic methodologies and their application to specific medical conditions. Other chapters will also touch upon areas that expand beyond proteomics, such as lipidomics and metabolomics.


Assuntos
Espectrometria de Massas , Proteômica , Biologia Computacional , Humanos , Mapeamento de Interação de Proteínas , Isoformas de Proteínas , Processamento de Proteína Pós-Traducional
8.
Adv Exp Med Biol ; 1140: 121-142, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31347045

RESUMO

Of the 25,000-30,000 human genes, about 2 % code for proteins. However, there are about 1-2 million protein entities. This is primarily due to alternative splicing, post-translational modifications (PTMs) or protein-protein interactions. Proteomics sets out to identify proteins, their sequence and known modifications as well as their quantitation in a biological sample for the purpose of understanding biological processes, protein cellular functions, and their physiological and pathological involvement in diseases.Proteins interact at the molecular level with other proteins, nucleic acids, lipids, carbohydrates and metabolites to perform numerous cellular activities. Protein complexes can consist of sets of more stably (stable PPIs) and less stably (transient PPIs) interacting proteins or combination of both. Here, we discuss the proteomics and non-proteomics approaches to study stable and transient PPIs.


Assuntos
Processamento de Proteína Pós-Traducional , Proteínas/análise , Proteômica , Humanos
9.
Adv Exp Med Biol ; 1140: 169-198, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31347048

RESUMO

Mass Spectrometry (MS) has revolutionized the way we study biomolecules, especially proteins, their interactions and posttranslational modifications (PTM). As such MS has established itself as the leading tool for the analysis of PTMs mainly because this approach is highly sensitive, amenable to high throughput and is capable of assigning PTMs to specific sites in the amino acid sequence of proteins and peptides. Along with the advances in MS methodology there have been improvements in biochemical, genetic and cell biological approaches to mapping the interactome which are discussed with consideration for both the practical and technical considerations of these techniques. The interactome of a species is generally understood to represent the sum of all potential protein-protein interactions. There are still a number of barriers to the elucidation of the human interactome or any other species as physical contact between protein pairs that occur by selective molecular docking in a particular spatiotemporal biological context are not easily captured and measured.PTMs massively increase the complexity of organismal proteomes and play a role in almost all aspects of cell biology, allowing for fine-tuning of protein structure, function and localization. There are an estimated 300 PTMS with a predicted 5% of the eukaryotic genome coding for enzymes involved in protein modification, however we have not yet been able to reliably map PTM proteomes due to limitations in sample preparation, analytical techniques, data analysis, and the substoichiometric and transient nature of some PTMs. Improvements in proteomic and mass spectrometry methods, as well as sample preparation, have been exploited in a large number of proteome-wide surveys of PTMs in many different organisms. Here we focus on previously published global PTM proteome studies in the Apicomplexan parasites T. gondii and P. falciparum which offer numerous insights into the abundance and function of each of the studied PTM in the Apicomplexa. Integration of these datasets provide a more complete picture of the relative importance of PTM and crosstalk between them and how together PTM globally change the cellular biology of the Apicomplexan protozoa. A multitude of techniques used to investigate PTMs, mostly techniques in MS-based proteomics, are discussed for their ability to uncover relevant biological function.


Assuntos
Espectrometria de Massas , Mapeamento de Interação de Proteínas/métodos , Processamento de Proteína Pós-Traducional , Proteômica/métodos , Humanos , Simulação de Acoplamento Molecular , Proteoma
10.
Adv Exp Med Biol ; 1140: 199-224, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31347049

RESUMO

There are only 30,000 human genes, which, according to the central dogma from biology, it means that there should be 30,000 mRNA and 30,000 proteins. However, there are at least 1-2 million protein entities that are expressed in a cell at a given time. This is primarily due to alternative splicing in different cells and tissues, which may lead to expression of different protein isoforms within one cell, but also different protein isoforms in different tissues. A new level of complexity of proteins and protein isoforms is then given by posttranslational modifications (PTMs) of proteins. Here, we discuss the PTMs in proteins and how they are identified by mass spectrometry and proteomics, with specific examples on identification of acetylation, phosphorylation, glycosylation, alkylation, hydroxinonenal-modification or assignment of intramolecular and intermolecular disulfide bridges.


Assuntos
Espectrometria de Massas , Processamento de Proteína Pós-Traducional , Proteômica , Acetilação , Alquilação , Glicosilação , Humanos , Fosforilação
11.
Adv Exp Med Biol ; 1140: 225-236, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31347050

RESUMO

Selection of high-producing lead and backup cell lines with high-fidelity primary structure is a major goal of cell line development of protein therapeutics. Conventional techniques for sequence variant analysis, such as mass spectrometry (MS) and next-generation sequencing (NGS) have limitations on the sample number and turnaround time, thus often are only applied at the final stages of development, where an undesired lead or backup clone could cause a significant delay in project timeline. Here we presented a high-throughput (HT) peptide mapping workflow which can be applied at early stages of cell line selection for testing of a batch of 30-40 clones within 2-week turnaround while reporting valuable information on sequence variants and posttranslational modifications (PTMs). The successful application of this workflow was demonstrated for two mAb programs. Multiple clones were removed from a total of 33 mAb-1 clones using various criteria: nine clones contained at least one >1% upregulated unknown peptide ions, 11 clones contained at least eight >0.1% upregulated unknowns, and six clones contained upregulated critical PTMs. For mAb-2, light chain (LC) sequence extension of approximately 30 amino acids were detected in 6 out of 36 clones at levels up to 11%. Besides, a Q to H mutation at ~30% was detected in the heavy chain (HC) of a single clone. Q to H mutation has mass change of 9.00 Da and failed to be detected by intact mass analysis. Rapid PTM quantitation also facilitated the selection of clones with desirable quality attributes, such as N-glycan profile. Hence, we demonstrated a risk-reducing strategy where abnormal clones could be detected at earlier stages of cell line selection, which should result in reduced and more predictable timeline of cell line development.


Assuntos
Anticorpos Monoclonais/química , Sequenciamento de Nucleotídeos em Larga Escala , Mapeamento de Peptídeos , Processamento de Proteína Pós-Traducional , Animais , Células CHO , Cricetinae , Cricetulus , Espectrometria de Massas
12.
Adv Exp Med Biol ; 1140: 753-769, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31347083

RESUMO

Mass spectrometry (MS) is the core for advanced methods in proteomic experiments. When effectively used, proteomics may provide extensive information about proteins and their post-translational modifications, as well as their interaction partners. However, there are also many problems that one can encounter during a proteomic experiment, including, but not limited to sample preparation, sample fractionation, sample analysis, data analysis & interpretation and biological significance. Here we discuss some of the problems that researchers should be aware of when performing a proteomic experiment.


Assuntos
Espectrometria de Massas , Proteínas/análise , Proteômica/métodos , Processamento de Proteína Pós-Traducional
13.
Adv Exp Med Biol ; 1157: 117-132, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31342440

RESUMO

Throughout evolution, eukaryotic cells have devised different mechanisms to cope with stressful environments. When eukaryotic cells are exposed to stress stimuli, they activate adaptive pathways that allow them to restore cellular homeostasis. Most types of stress stimuli have been reported to induce a decrease in overall protein synthesis accompanied by induction of alternative mechanisms of mRNA translation initiation. Here, we present well-studied and recent examples of such stress responses and the alternative translation initiation mechanisms they induce, and discuss the consequences of such regulation for cell homeostasis and oncogenic transformation.


Assuntos
Neoplasias , Iniciação Traducional da Cadeia Peptídica , Biossíntese de Proteínas , Estresse Fisiológico , Humanos , Neoplasias/genética , Biossíntese de Proteínas/genética , Processamento de Proteína Pós-Traducional , Proteômica , Estresse Fisiológico/genética
14.
Biomed Khim ; 65(3): 251-258, 2019 Apr.
Artigo em Russo | MEDLINE | ID: mdl-31258150

RESUMO

The relative differences between post-translational modifications (PTM) of proteins in blood plasma samples of patients with cerebral ischemia (CI) and healthy people were investigated using of the method of label-free comparative proteomic analysis based on the technology of tandem HPLC-MS/MS. For PTM detection we used multiple MS/MS search in the database Mascot for variable PTM and Progenesis LS-MS software. In the CI plasma samples, we observed an increase in the proportion of peptides with such PTM as phosphorylation of serine, threonine, and tyrosine, acetylation of lysine and protein N-term, ubiquitination of lysine and deamidation of glutamine related to clinically significant processes were revealed.


Assuntos
Isquemia Encefálica/sangue , Processamento de Proteína Pós-Traducional , Proteoma , Cromatografia Líquida de Alta Pressão , Humanos , Proteômica , Espectrometria de Massas em Tandem
15.
Gene ; 712: 143963, 2019 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-31279706

RESUMO

BACKGROUND: The aim of this study was to identify the expression of LIM and calponin-homology domains 1 (LIMCH1) in lung cancer and normal tissues, to determine the interaction between LIMCH1 and HUWE1 in regulating p53 stability. METHODS: The expression of LIMCH1 was detected by the Oncomine and Cancer Genome Atlas databases. Expression of LIMCH1 mRNA was identified using qRT-PCR. In transfected human lung cancer cells, co-immunoprecipitation experiments were performed. The mechanism that HUWE1 sustained lung cancer malignancy was verified by western blotting. The proliferation of tranfected cells was assessed by CCK-8 assay and colony formation. RESULTS: Bioinformatic data and e TCGA database suggested LIMCH1 mRNA levels in tumor tissues were down-regulated compared to tumor adjacent tissues. We found low expression of LIMCH1 mRNA in tumor sites and tumor cell line. Exogenous expression of LIMCH1 interacts with HUWE1 promotes expression of p53. Use of siRNA or shRNA against LIMCH1 resulted in decreased p53 protein levels. LIMCH1 deletion lead to enhance of p53 ubiquitination and protein expression of p53 and substrate p21, puma. Growth curve showed that LIMCH1 deletion significantly promoted the proliferation of A549 cells. CONCLUSIONS: LIMCH1 was a negative regulator and indicated a new molecular mechanism for the pathogenesis of lung cancer via modulating HUWE1 and p53.


Assuntos
Regulação Neoplásica da Expressão Gênica , Proteínas com Domínio LIM/metabolismo , Neoplasias Pulmonares/metabolismo , Proteína Supressora de Tumor p53/metabolismo , Proteínas Supressoras de Tumor/metabolismo , Ubiquitina-Proteína Ligases/metabolismo , Células A549 , Idoso , Linhagem Celular Tumoral , Proliferação de Células , Biologia Computacional , Regulação para Baixo , Feminino , Perfilação da Expressão Gênica , Humanos , Proteínas com Domínio LIM/genética , Neoplasias Pulmonares/genética , Masculino , Pessoa de Meia-Idade , Processamento de Proteína Pós-Traducional , Interferência de RNA , RNA Interferente Pequeno/metabolismo , Proteína Supressora de Tumor p53/genética , Proteínas Supressoras de Tumor/genética , Ubiquitina-Proteína Ligases/genética , Ubiquitinação
16.
Nat Commun ; 10(1): 2955, 2019 07 04.
Artigo em Inglês | MEDLINE | ID: mdl-31273203

RESUMO

Dendritic cells (DCs), a vital component of the innate immune system, are considered to lack antigen specificity and be devoid of immunological memory. Strategies that can induce memory-like responses from innate cells can be utilized to elicit protective immunity in immune deficient persons. Here we utilize an experimental immunization strategy to modulate DC inflammatory and memory-like responses against an opportunistic fungal pathogen that causes significant disease in immunocompromised individuals. Our results show that DCs isolated from protectively immunized mice exhibit enhanced transcriptional activation of interferon and immune signaling pathways. We also show long-term memory-like cytokine responses upon subsequent challenge with the fungal pathogen that are abrogated with inhibitors of specific histone modifications. Altogether, our study demonstrates that immunization strategies can be designed to elicit memory-like DC responses against infectious disease.


Assuntos
Células Dendríticas/imunologia , Memória Imunológica , Animais , Criptococose/imunologia , Criptococose/microbiologia , Cryptococcus/fisiologia , Células Dendríticas/microbiologia , Feminino , Histonas/metabolismo , Imunidade Inata , Inflamação/genética , Inflamação/patologia , Interferon gama/metabolismo , Pulmão/imunologia , Pulmão/microbiologia , Camundongos Endogâmicos BALB C , Fenótipo , Processamento de Proteína Pós-Traducional , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Vacinação
17.
Biochemistry (Mosc) ; 84(Suppl 1): S206-S224, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31213203

RESUMO

Reactive carbonyl compounds (RCC) are a group of compounds with clearly pronounced electrophilic properties that facilitate their spontaneous reactions with numerous nucleophilic reaction sites in proteins, lipids, and nucleic acids. The biological functions of RCC are determined by their concentration and governed by the hormesis (biphasic reaction) principle. At low concentrations, RCC act as signaling molecules activating defense systems against xenobiotics and oxidizers, and at high concentrations, they exhibit the cytotoxic effect. RCC participate in the formation of cell adaptive response via intracellular signaling pathways involving regulation of gene expression and cytoplasmic mechanisms related to the structure-functional rearrangements of proteins. Special attention in this review is given to the functioning of electrophiles as mediators of cell general adaption syndrome manifested as the biphasic response. The hypothesis is proposed that electrophilic signaling can be a proto-signaling system.


Assuntos
Aldeídos/metabolismo , Radicais Livres/metabolismo , Cetonas/metabolismo , Mutagênese/fisiologia , Estresse Oxidativo/fisiologia , Transdução de Sinais/fisiologia , Animais , Humanos , Oxirredução , Processamento de Proteína Pós-Traducional
18.
Adv Exp Med Biol ; 1073: 23-56, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31236838

RESUMO

The preanalytical phase of saliva proteomics/peptidomics, which includes sample collection, handling, and storage, represents a major challenge for any researcher that envisions sensitive and high-throughput analyses, coupled to well-controlled study design. The methodology used to collect saliva determines the contribution of each salivary gland to saliva composition with impact on data retrieved from proteomics/peptidomics. The awareness of the importance of this step in the analysis of saliva has prompted the proposal of several collection strategies. Moreover, numerous commercial devices are available in an attempt to routine the procedures. However, whatever the chosen method, procedures should be kept simple, standardized to get better reproducibility and repeatability on saliva proteomics analysis. Sample preservation is also a key step in saliva proteomics/peptidomics, and the implemented lab procedures should avoid posttranslational modifications such as proteolysis, as well as protein precipitation.In this chapter, we provide recommendations for saliva sampling and preservation, envisaging to standardize procedures that facilitate the use of saliva in clinical applications and the translation of proteomics data to diagnosis and/or definition of therapeutic targets.


Assuntos
Proteômica , Saliva/química , Manejo de Espécimes/métodos , Humanos , Processamento de Proteína Pós-Traducional , Reprodutibilidade dos Testes
19.
Gene ; 711: 143934, 2019 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-31228540

RESUMO

Phytopathogenic fungi secrete a wide range of enzymes to penetrate and colonize host tissues. Of them protease activity is reported to increase disease aggressiveness in the plant. With the aim to explore the reason of the higher infection potential of proteases, we have compared several genomic and proteomic attributes among different hydrolytic enzymes coded by five pathogenic fungal species which are the potent infectious agents of plant. Categorizing the enzymes into four major groups, namely protease, lipase, amylase and cell-wall degraders, we observed that proteases are evolutionary more conserved, have higher expression levels, contain more hydrophobic buried residues, short linear motifs and post-translational modified (PTM) sites than the other three groups of enzymes. Again, comparing these features of protease between pathogenic and non-pathogenic Aspergillus sps, we have hypothesized that protein structural properties could play significant roles in imposing infection potency to the fungal proteases.


Assuntos
Aspergillus/patogenicidade , Biologia Computacional/métodos , Peptídeo Hidrolases/química , Peptídeo Hidrolases/genética , Aspergillus/classificação , Aspergillus/genética , Simulação por Computador , Sequência Conservada , Proteínas Fúngicas/química , Proteínas Fúngicas/genética , Perfilação da Expressão Gênica/métodos , Regulação Neoplásica da Expressão Gênica , Interações Hidrofóbicas e Hidrofílicas , Filogenia , Conformação Proteica , Processamento de Proteína Pós-Traducional , Proteômica/métodos
20.
Cell Mol Life Sci ; 76(15): 2871-2872, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31177294

RESUMO

Protein post-translational modifications (PTMs) have long been a topic of intensive investigation. Covalent additions to the 20 genetically encoded amino acids can alter protein interactions and can even change enzymatic function. In eukarya, PTMs can amplify both the complexity and functional paradigms of the cellular environment. Therefore, PTMs have been of substantial research interest, both for understanding fundamental mechanisms and to provide insight into drug design. Indeed, targeting proteins involved in writing, reading, and erasing PTMs important for human pathologies are some of the most fruitful avenues of drug discovery. In this multi-author review, we explore exciting new work on lysine and arginine methylation, molecular and structural understanding of some of the lysine and arginine methyltransferases (KMTs and PRMTs, respectively), novel insights into nucleic acid methylation, and how the enzymes responsible for writing these PTMs and readers responsible for recognizing these PTMs could be drugged. Here, we introduce the background and the topics covered in this issue.


Assuntos
Processamento de Proteína Pós-Traducional , Arginina/metabolismo , Histona-Lisina N-Metiltransferase/metabolismo , Histonas/metabolismo , Humanos , Lisina/metabolismo , Metilação , Proteína-Arginina N-Metiltransferases/metabolismo
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