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1.
Phys Chem Chem Phys ; 21(35): 18811-18815, 2019 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-31468044

RESUMO

Recent experiments have reported that diffusion of enzymes can be enhanced in the presence of their substrates. Using a fluctuating dumbbell model of enzymes, it has been argued that such an enhancement can be rationalized by the reduction of the enzyme size and by the suppression of the hydrodynamically coupled conformational fluctuations, induced by binding a substrate or an inhibitor to the enzyme [Nano Lett. 2017, 17, 4415]. Herein, we critically examine these expectations via extensive Brownian dynamics simulations of a similar model. The numerical results show that neither of the two mechanisms can cause an enhancement comparable to that reported experimentally, unless very large, physically counter-intuitive, enzyme deformations are invoked.


Assuntos
Enzimas/química , Enzimas/metabolismo , Simulação de Dinâmica Molecular , Difusão , Modelos Químicos
2.
Phys Rev Lett ; 123(3): 038101, 2019 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-31386470

RESUMO

Synthesis of biopolymers such as DNA, RNA, and proteins are biophysical processes aided by enzymes. The performance of these enzymes is usually characterized in terms of their average error rate and speed. However, because of thermal fluctuations in these single-molecule processes, both error and speed are inherently stochastic quantities. In this Letter, we study fluctuations of error and speed in biopolymer synthesis and show that they are in general correlated. This means that, under equal conditions, polymers that are synthesized faster due to a fluctuation tend to have either better or worse errors than the average. The error-correction mechanism implemented by the enzyme determines which of the two cases holds. For example, discrimination in the forward reaction rates tends to grant smaller errors to polymers with faster synthesis. The opposite occurs for discrimination in monomer rejection rates. Our results provide an experimentally feasible way to identify error-correction mechanisms by measuring the error-speed correlations.


Assuntos
Biopolímeros/biossíntese , Enzimas/química , Enzimas/metabolismo , Biopolímeros/química , DNA/biossíntese , DNA/química , Humanos , Modelos Biológicos , Modelos Químicos , RNA/biossíntese , RNA/química
4.
World J Microbiol Biotechnol ; 35(9): 131, 2019 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-31432251

RESUMO

Cholesterol is a C27-sterol employed as starting material for the synthesis of valuable pharmaceutical steroids and precursors. The microbial transformations of cholesterol have been widely studied, since they are performed with high regio- and stereoselectivity and allow the production of steroidal compounds which are difficult to synthesize by classical chemical methods. In recent years, ongoing research is being conducted to discover novel biocatalysts and to develop biotechnological processes to improve existing biocatalysts and biotransformation reactions. The main objective of this review is to present the most remarkable advances in fungal and bacterial transformation of cholesterol, focusing on the different types of microbial reactions and biocatalysts, biotransformation products, and practical aspects related to sterol dispersion improvement, covering literature since 2000. It reviews the conversion of cholesterol by whole-cell biocatalysts and by purified enzymes that lead to various structural modifications, including side chain cleavage, hydroxylation, dehydrogenation/reduction, isomerization and esterification. Finally, approaches used to improve the poor solubility of cholesterol in aqueous media, such as the use of different sterol-solubilizing agents or two-phase conversion system, are also discussed.


Assuntos
Bactérias/metabolismo , Biotecnologia/métodos , Colesterol/metabolismo , Fungos/metabolismo , Bactérias/genética , Bactérias/crescimento & desenvolvimento , Biotecnologia/tendências , Biotransformação , Enzimas/metabolismo , Fungos/genética , Fungos/crescimento & desenvolvimento
5.
Phys Rev Lett ; 122(23): 238102, 2019 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-31298900

RESUMO

The enormous catalytic power of natural enzymes relies on the ability to overcome the bottleneck event in the enzymatic cycle, yet the underlying physical mechanisms are not fully understood. Here, by performing molecular simulations of the whole enzymatic cycle for a model multisubstrate enzyme with a dynamic energy landscape model, we show that multisubstrate enzymes can utilize steric frustration to facilitate the rate-limiting product-release step. During the enzymatic cycles, the bottleneck product is actively squeezed out by the binding of a new substrate at the neighboring site through the population of a substrate-product cobound complex, in which the binding pockets are frustrated due to steric incompatibility. Such steric frustration thereby enables an active mechanism of product release driven by substrate-binding energy, facilitating the enzymatic cycle.


Assuntos
Enzimas/química , Enzimas/metabolismo , Modelos Químicos , Adenilato Quinase/química , Adenilato Quinase/metabolismo , Modelos Moleculares , Conformação Proteica , Relação Estrutura-Atividade , Termodinâmica
6.
Food Chem ; 298: 124928, 2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31272053

RESUMO

Sonication can significantly enhance amino acids (AAs) release to accelerate maturation during short-term and low-salt soy sauce fermentation. Here, sonication was applied at 68 kHz (60 W/L/10 min/8 circles) to determine its effects on the taste during long-term and high-salt soy sauce fermentation. The possible mechanisms were explored by analyzing differences in enzymes profile, proximate indices, molecular weight distribution of peptides, AAs composition and microstructures of sonicated moromis and their controls. Sonication greatly elevated levels of organic taste compounds ranging from 8.4% to 22.2%, but lowered levels of NaCl (6.0%), peptides ≤ 1 kDa (5.2%), histidine (20.5%) and glutamic acid (3.4%). Compared to its controls, sonicated raw soy sauces also had a more harmonious and palatable taste. Increased enzymes' activities and formation of more surface area and reaction sites in sonicated moromis might be the possible mechanisms for sonication to elevate levels of taste compounds and sensory quality of soy sauce.


Assuntos
Alimentos Fermentados , Sonicação/métodos , Alimentos de Soja , Paladar , Aminoácidos/análise , Enzimas/química , Enzimas/metabolismo , Fermentação , Ácido Glutâmico/análise , Humanos , Peso Molecular , Peptídeos/análise , Peptídeos/química , Cloreto de Sódio na Dieta/análise
7.
BMC Bioinformatics ; 20(1): 386, 2019 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-31291905

RESUMO

BACKGROUND: Mathematical models of biological networks can provide important predictions and insights into complex disease. Constraint-based models of cellular metabolism and probabilistic models of gene regulatory networks are two distinct areas that have progressed rapidly in parallel over the past decade. In principle, gene regulatory networks and metabolic networks underly the same complex phenotypes and diseases. However, systematic integration of these two model systems remains a fundamental challenge. RESULTS: In this work, we address this challenge by fusing probabilistic models of gene regulatory networks into constraint-based models of metabolism. The novel approach utilizes probabilistic reasoning in BN models of regulatory networks serves as the "glue" that enables a natural interface between the two systems. Probabilistic reasoning is used to predict and quantify system-wide effects of perturbation to the regulatory network in the form of constraints for flux variability analysis. In this setting, both regulatory and metabolic networks inherently account for uncertainty. Applications leverage constraint-based metabolic models of brain metabolism and gene regulatory networks parameterized by gene expression data from the hippocampus to investigate the role of the HIF-1 pathway in Alzheimer's disease. Integrated models support HIF-1A as effective target to reduce the effects of hypoxia in Alzheimer's disease. However, HIF-1A activation is far less effective in shifting metabolism when compared to brain metabolism in healthy controls. CONCLUSIONS: The direct integration of probabilistic regulatory networks into constraint-based models of metabolism provides novel insights into how perturbations in the regulatory network may influence metabolic states. Predictive modeling of enzymatic activity can be facilitated using probabilistic reasoning, thereby extending the predictive capacity of the network. This framework for model integration is generalizable to other systems.


Assuntos
Doença de Alzheimer/metabolismo , Redes e Vias Metabólicas , Modelos Biológicos , Modelos Estatísticos , Teorema de Bayes , Enzimas/metabolismo , Redes Reguladoras de Genes , Humanos , Fenótipo , Transdução de Sinais
8.
Chem Biol Interact ; 309: 108704, 2019 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-31211951

RESUMO

Progress curves for competing substrates were analyzed to investigate the effect of an "invisible" substrate (B) on the time-course of enzyme-catalyzed substrate degradation of a "visible" (reporter) substrate (A). Rate equations were integrated for Michaelis-Menten kinetics and in the case of activation or inhibition of degradation of A by excess of substrate B. The shape of progress curves depends on the ratio of specificity constants (kcat/Km)B/A, the competition matrix (R). Mathematical solutions exist for R ≫ 1, R = 1, R ≪ 1. Working at constant reporter substrate A concentration, from the shape of progress curves (sigmoidal or non-sigmoidal), it is possible to define the type of competitor (B), and from the dependence of retardation time (at 90% completion of A, and at inflexion point for sigmoid-like shaped progress curves) on "invisible" substrate B concentration, it is therefore possible to access to catalytic parameters, and/or to titrate enzyme active sites. This competing substrate approach is suitable for investigating new substrates and reversible inhibitors of toxicological and pharmacological interest, investigating enzyme promiscuity, screening of enzymes degrading numerous compounds, and mining new enzymes of medical or biotechnological interest.


Assuntos
Enzimas/metabolismo , Biocatálise , Cinética , Modelos Teóricos , Especificidade por Substrato
9.
Mar Pollut Bull ; 142: 408-418, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31232318

RESUMO

Oil and gas exploration and marine transport in the Arctic region have put the focus on the ecological risk of the possibly exposed organisms. In the present study, the impacts of sea ice, extreme light regime, various polar region-specific physiological characteristics in polar cod (Boreogadus saida) and their effects on xenobiotic distribution and metabolism are studied. A Bayesian belief network is used to model individual fish toxicity. The enzyme activity in the fish liver and other pertinent organs is used as a proxy for cellular damage and repair and is subsequently linked to toxicity in polar cod. Seasonal baseline variation in enzyme production is also taken into consideration. The model estimates the probability of exposure concentration to cause cytotoxicity and circumvents the need to use the traditionally obtained No Observed Effect Concentration (NOEC). Instead, it uses biotransformation enzyme activity as a basis to estimate the probability of individual cell damages.


Assuntos
Ecotoxicologia/métodos , Gadiformes/metabolismo , Modelos Teóricos , Hidrocarbonetos Policíclicos Aromáticos/toxicidade , Poluentes Químicos da Água/toxicidade , Animais , Regiões Árticas , Teorema de Bayes , Biotransformação , Biomarcadores Ambientais , Enzimas/metabolismo , Gadiformes/fisiologia , Fígado/efeitos dos fármacos , Fígado/metabolismo , Poluição por Petróleo/efeitos adversos , Hidrocarbonetos Policíclicos Aromáticos/farmacocinética , Medição de Risco , Estações do Ano , Poluentes Químicos da Água/farmacocinética , Xenobióticos/farmacocinética , Xenobióticos/toxicidade
10.
Food Chem ; 297: 124955, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31253342

RESUMO

This study aimed to investigate the effect of hydrogen peroxide (H2O2) on membrane lipids metabolism and its relation to pulp breakdown development of longan fruit during postharvest storage. Compared to the control longans, H2O2-treated longans showed higher pulp breakdown index, cell membrane permeability, and activities of phospholipase D (PLD), lipase and lipoxygenase (LOX). Moreover, H2O2-treated longans maintained higher levels of pulp phosphatidic acid (PA) and saturated fatty acids (SFA). However, H2O2-treated longans exhibited lower levels of pulp phosphatidylcholine (PC), phosphatidylinositol (PI) and unsaturated fatty acids (USFA), lower index of unsaturated fatty acids (IUFA), and lower ratio of USFA to SFA (U/S). These findings demonstrated that H2O2 caused the increased activities of enzymes involving in membrane lipids degradation and the accelerated decompositions of membrane USFA and phospholipids in longan pulp, which eventually triggered the destruction of the pulp cell membrane structure and the development of pulp breakdown in longans during storage.


Assuntos
Enzimas/metabolismo , Frutas/química , Peróxido de Hidrogênio/farmacologia , Lipídeos de Membrana/metabolismo , Sapindaceae/química , Enzimas/química , Ácidos Graxos/análise , Ácidos Graxos/química , Armazenamento de Alimentos , Frutas/efeitos dos fármacos , Frutas/metabolismo , Peróxido de Hidrogênio/química , Lipase/química , Lipase/metabolismo , Metabolismo dos Lipídeos/efeitos dos fármacos , Lipoxigenase/química , Lipoxigenase/metabolismo , Lipídeos de Membrana/química , Fosfolipase D/metabolismo , Fosfolipídeos/química , Fosfolipídeos/metabolismo , Proteínas de Plantas/química , Proteínas de Plantas/metabolismo , Sapindaceae/efeitos dos fármacos , Sapindaceae/metabolismo
11.
Aquat Toxicol ; 212: 241-246, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31150951

RESUMO

Nowadays, eutrophication is a very popular environmental problem in numerous waters around the world. The main reason of eutrophication is the enrichment of the nutrient, which results in the excessive growth of phytoplankton and some of them are toxic and harmful. Fortunately, some studies have shown that some bivalves can filter the overgrown phytoplankton in water, which may alleviate water eutrophication. However, the physiological effects of toxic cyanobacteria on filter feeding animal have not been clarified very well. In this experiment, digestive enzyme activities in Hyriopsis cumingii exposed to different concentrations of the toxic Microcystis aeruginosa (0, 5 * 105 and 5 *106 cell ml-1) at two dissolved oxygen (DO) levels (6 and 2 mg l-1) for 14 days were investigated. Toxic M. aeruginosa significantly affected all digestive enzyme activities throughout the experiment. At high toxic M. aeruginosa concentration, the activities of cellulase, amylase and lipase in digestive gland and stomach were significantly increased (P<0.05). However, hypoxia reduced the activities of cellulase, amylase and lipase in digestive gland and stomach. Conflicting effects were observed between toxic M. aeruginosa and DO in most digestive enzyme activities during the exposure period. Therefore, it is not conducive for the digestion and absorption of M. aeruginosa in H. cumingii under hypoxic conditions. H. cumingii is tolerant to toxic M. aeruginosa and may remove toxic cyanobacteria from waters under normal DO conditions.


Assuntos
Bivalves/efeitos dos fármacos , Microcistinas/toxicidade , Microcystis/química , Anaerobiose/fisiologia , Animais , Bivalves/enzimologia , Bivalves/fisiologia , Ativação Enzimática/efeitos dos fármacos , Enzimas/metabolismo , Eutrofização , Oxigênio/metabolismo , Poluentes Químicos da Água/toxicidade
12.
Chem Soc Rev ; 48(13): 3497-3512, 2019 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-31214680

RESUMO

Icosahedral carboranes in medicine are still an emerging class of compounds with potential beneficial applications in drug design. These highly hydrophobic clusters are potential "new keys for old locks" which open up an exciting field of research for well-known, but challenging important therapeutic substrates, as demonstrated by the numerous examples discussed in this review.


Assuntos
Boranos/química , Animais , Boranos/farmacologia , Desenho de Drogas , Enzimas/metabolismo , Humanos , Interações Hidrofóbicas e Hidrofílicas , Fator 1 Induzível por Hipóxia/metabolismo , Ligantes , Receptores Androgênicos/metabolismo , Receptores de Calcitriol/metabolismo , Receptores Estrogênicos/metabolismo , Receptores Purinérgicos/metabolismo
13.
Chem Asian J ; 14(16): 2780-2784, 2019 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-31207187

RESUMO

The Acinetobacter sp. strain M isolated from a contaminated soil sample in Jiangsu Province of China was found to be able to degrade perfluorooctane sulfonamide (PFOSA) effectively. Fluoride anion (F- ) released from PFOSA degradation was detected by ion chromatography, and showed positive correlation to the growth curve of Acinetobacter sp. strain M. The PFOSA degradation efficiency of strain M was approximately 27 %, as assessed by GC analysis. It was shown that enzymes localized outside of cells of Acinetobacter sp. strain M catalyzed the degradation of PFOSA. This further indicates a possibly new (multi-step/pathway) mechanism for PFOSA degradation. It revealed that the extracellular enzyme of the Acinetobacter strain M preferentially cleaves carbon-carbon and carbon-fluorine bonds instead of destroying the carbon-sulfur bond. The growth condition for Acinetobacter sp. strain M was optimized at 30 °C and pH 7.0 in the presence of 2000 mg L-1 of PFOSA and 0.5 % (v/v) of Tween-20. The optimal PFOSA degradation time was found to be 12 h, with a degradation efficiency of 76 % by extracellular enzymes in strain M as determined by GC analysis. The result may provide potential applications for biodegradition of perfluoro organic compounds, such as derivatives of perfluorooctane (C8).


Assuntos
Acinetobacter/metabolismo , Enzimas/metabolismo , Fluorcarbonetos/metabolismo , Sulfonamidas/metabolismo , Acinetobacter/enzimologia , Acinetobacter/crescimento & desenvolvimento , Cromatografia Gasosa-Espectrometria de Massas , Microbiologia do Solo
14.
Food Chem ; 295: 138-146, 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31174742

RESUMO

This study investigates the impact of different gelatinization characteristics of small and large barley starch granules on their enzymatic hydrolysis and sugar production during mashing. Therefore, a barley malt suspension was consecutively incubated at 45, 62, 72 and 78 °C to monitor starch behavior and enzymatic starch hydrolysis and sugar production. The combination of microscopic and rapid visco analyses showed that small starch granules persisted longer in the system and were present non-gelatinized at temperatures higher than 62 °C. HPAEC-PAD analysis showed that 8% of the total amount of starch, predominantly small granules, gelatinized at temperatures between 62 °C and 78 °C. Due to their delayed gelatinization in this system, their enzymatic hydrolysis yielded relatively more dextrins compared to what was observed for large granules. It was concluded that small granules should be taken into account when optimizing enzymatic hydrolysis of barley starch, like in brewing, distilling or bio-ethanol production.


Assuntos
Hordeum/metabolismo , Amido/química , Açúcares/metabolismo , Varredura Diferencial de Calorimetria , Dextrinas/metabolismo , Enzimas/metabolismo , Hidrólise , Tamanho da Partícula , Amido/metabolismo , Temperatura Ambiente , Viscosidade
15.
Chemosphere ; 233: 207-215, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31173958

RESUMO

Rain garden is a typical facility with many applications in urban low impact development (LID). It plays an important role in regulating runoff water quantity and quality. Two rain gardens with the discharge ratios of 20:1 and 15:1 were used as studied facilities. Seven soil sampling events were conducted from April 2017 to February 2019 to study the influences of stormwater concentration infiltration in rain gardens on soil nitrogen (N), phosphorus (P) and TOC and their relations with enzymes. The results showed that the contents of soil TN and NO2-N + TON in gardens gradually decreased with time, while those of NH3-N and TP increased with time. The content of NO3-N varied greatly with time, and there was no obvious rule. TOC increased first and then decreased. Vertical distributions of N, P and TOC showed that the contents of NH3-N, NO2-N + TON and TN at 0-50 cm were high, so the upper soil was the sensitive area to the influence of stormwater concentration infiltration in rain gardens. The content of NH3-N decreased gradually with the increase of soil depth, but those of NO3-N and TP increased with the soil depth. Therefore, NO3-N and TP migrated down with water infiltration in soil, and preventing NO3-N and P leaching was critical for effective N and P removal though rain gardens. Soil urease (SU), sucrose (SS), protease (SP) and acid phosphatase (SAP) had a good linear relationship with N, P and TOC, and R2were all greater than 0.5.


Assuntos
Carbono/química , Enzimas/metabolismo , Nitrogênio/análise , Fósforo/análise , Solo/química , Carbono/análise , China , Monitoramento Ambiental , Enzimas/química , Jardins , Nitrogênio/química , Fósforo/química , Chuva
16.
Nature ; 570(7760): 172-173, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31182827
17.
J Zoo Wildl Med ; 50(1): 45-54, 2019 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-31120661

RESUMO

Plasma biochemical enzymes are commonly assayed as part of a diagnostic evaluation for zoological species, but their interpretation is complicated by a lack of knowledge about tissue of origin in many reptiles. This study evaluated tissue specificity of six biochemical enzymes (alanine aminotransferase [ALT], aspartate aminotransferase [AST], alkaline phosphatase [ALP], creatine kinase [CK], gamma-glutamyl transferase [GGT], and glutamate dehydrogenase [GLDH]) in 10 tissues (skeletal muscle, cardiac muscle, lung, liver, gallbladder, pancreas, gastrointestinal tract, kidney, spleen, and reproductive tract) from 10 free-living eastern box turtles (Terrapene carolina carolina). CK activity was highest in skeletal muscle, cardiac muscle, and gastrointestinal tract; GLDH and ALT activities were highest in liver, kidney, and gallbladder; ALP and GGT activities were elevated in kidney and gastrointestinal tract; and AST was relatively nonspecific, with significantly higher activity in the cardiac muscle, liver, kidney, skeletal muscle, and gallbladder compared to other tissues (P < 0.05). These results serve as a first step toward improving clinical interpretation of plasma biochemistry panels in box turtles.


Assuntos
Enzimas/metabolismo , Tartarugas/metabolismo , Alternativas aos Testes com Animais , Animais , Feminino , Masculino , Especificidade de Órgãos
18.
Chemosphere ; 229: 471-480, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31091488

RESUMO

The functional stability of soil enzymes is fundamental to the sustainability of soil biochemical processes and is affected by many environmental stressors. This study focused on the influences of long-term arsenic (As) contamination on soil enzyme functional stability: the resistance (ratio of the disturbed to control) and resilience (integrated recovery rate) of soil enzyme activities (ß-glucosidase, urease, acid phosphatase, fluorescein diacetate (FDA) hydrolase) over 30 days incubation after an experimental heat disturbance (50 oC for 18 h). Results showed that the resistance of soil enzymes to heat disturbance differed among the enzyme types and followed the order: urease > ß-glucosidase > acid phosphatase > FDA hydrolase. Urease activity was generally not affected and showed high stability against heat disturbance. The ß-glucosidase activity recovered to the control level by 30 days, while 80% and 90% recovery on average occurred for acid phosphatase and FDA hydrolase, respectively. Long-term As contamination altered soil enzyme functional resistance and resilience to heat disturbance and resulted in three kinds of responses: (i) no apparent alteration (urease); (ii) moderate As contamination increased enzyme heat resistance (ß-glucosidase); (iii) the resistance and resilience decreased with increasing As concentration (acid phosphatase and FDA hydrolase). The results demonstrated that different enzyme-catalytic biochemical processes have different functional stabilities under combined As and heat disturbance, and the negative changes in the soil enzyme activity led to losses in soil functions. Our study provides further evidence on the impacts of heavy metal/metalloid on soil enzyme functional stability in response to additional disturbance.


Assuntos
Arsênico/toxicidade , Enzimas/química , Poluentes do Solo/toxicidade , Solo/química , Arsênico/análise , China , Estabilidade Enzimática , Enzimas/metabolismo , Temperatura Alta , Microbiologia do Solo , Poluentes do Solo/análise
19.
Anal Bioanal Chem ; 411(17): 3721-3729, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31139859

RESUMO

Combining mass spectrometry (MS) with surface plasmon resonance (SPR) makes it possible to identify the chemical structures of the interacting molecules studied by SPR. Different approaches for coupling surface plasmon resonance sensors to mass spectrometry were developed. This article aims to summarize the established approaches and their applications to study biomolecular interactions. Three representative interactions were reviewed: protein-protein interactions, enzyme-substrate/inhibitor interactions, and protein-small molecule interactions.


Assuntos
Espectrometria de Massas/métodos , Ressonância de Plasmônio de Superfície/métodos , Enzimas/metabolismo , Conformação Proteica , Domínios e Motivos de Interação entre Proteínas , Proteínas/metabolismo , Especificidade por Substrato
20.
Nat Commun ; 10(1): 2133, 2019 05 13.
Artigo em Inglês | MEDLINE | ID: mdl-31086177

RESUMO

Polycomb (PcG) and Trithorax (TrxG) group proteins give stable epigenetic memory of silent and active gene expression states, but also allow poised states in pluripotent cells. Here we systematically address the relationship between poised, active and silent chromatin, by integrating 73 publications on PcG/TrxG biochemistry into a mathematical model comprising 144 nucleosome modification states and 8 enzymatic reactions. Our model predicts that poised chromatin is bistable and not bivalent. Bivalent chromatin, containing opposing active and silent modifications, is present as an unstable background population in all system states, and different subtypes co-occur with active and silent chromatin. In contrast, bistability, in which the system switches frequently between stable active and silent states, occurs under a wide range of conditions at the transition between monostable active and silent system states. By proposing that bistability and not bivalency is associated with poised chromatin, this work has implications for understanding the molecular nature of pluripotency.


Assuntos
Cromatina/metabolismo , Epigênese Genética/fisiologia , Modelos Biológicos , Proteínas do Grupo Polycomb/metabolismo , Proteínas Cromossômicas não Histona/metabolismo , Proteínas de Drosophila/metabolismo , Enzimas/metabolismo , Código das Histonas/fisiologia , Histona-Lisina N-Metiltransferase/metabolismo , Histonas/metabolismo , Proteína de Leucina Linfoide-Mieloide/metabolismo , Nucleossomos/metabolismo
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