Base de dados : MEDLINE
Pesquisa : D02.092.146.125 [Categoria DeCS]
Referências encontradas : 2017 [refinar]
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  1 / 2017 MEDLINE  
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[PMID]:28833802
[Au] Autor:Nemergut M; Zoldák G; Schaefer JV; Kast F; Miskovský P; Plückthun A; Sedlák E
[Ad] Endereço:Department of Biophysics, P.J. Safárik University, Jesenna 5, Kosice, 041 54, Slovakia.
[Ti] Título:Analysis of IgG kinetic stability by differential scanning calorimetry, probe fluorescence and light scattering.
[So] Source:Protein Sci;26(11):2229-2239, 2017 Nov.
[Is] ISSN:1469-896X
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Monoclonal antibodies of the immunoglobulin G (IgG) type have become mainstream therapeutics for the treatment of many life-threatening diseases. For their successful application in the clinic and a favorable cost-benefit ratio, the design and formulation of these therapeutic molecules must guarantee long-term stability for an extended period of time. Accelerated stability studies, e.g., by employing thermal denaturation, have the great potential for enabling high-throughput screening campaigns to find optimal molecular variants and formulations in a short time. Surprisingly, no validated quantitative analysis of these accelerated studies has been performed yet, which clearly limits their application for predicting IgG stability. Therefore, we have established a quantitative approach for the assessment of the kinetic stability over a broad range of temperatures. To this end, differential scanning calorimetry (DSC) experiments were performed with a model IgG, testing chaotropic formulations and an extended temperature range, and they were subsequently analyzed by our recently developed three-step sequential model of IgG denaturation, consisting of one reversible and two irreversible steps. A critical comparison of the predictions from this model with data obtained by an orthogonal fluorescence probe method, based on 8-anilinonaphthalene-1-sulfonate binding to partially unfolded states, resulted in very good agreement. In summary, our study highlights the validity of this easy-to-perform analysis for reliably assessing the kinetic stability of IgGs, which can support accelerated formulation development of monoclonal antibodies by ranking different formulations as well as by improving colloidal stability models.
[Mh] Termos MeSH primário: Naftalenossulfonato de Anilina/química
Corantes Fluorescentes/química
Imunoglobulina G/química
[Mh] Termos MeSH secundário: Estabilidade de Medicamentos
Células HEK293
Seres Humanos
Cinética
Ligação Proteica
Desnaturação Proteica
Dobramento de Proteína
Estabilidade Proteica
Proteínas Recombinantes/química
Espectrometria de Fluorescência
Temperatura Ambiente
Ureia/química
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (8-anilino-1-naphthalenesulfonic acid); 0 (Anilino Naphthalenesulfonates); 0 (Fluorescent Dyes); 0 (Immunoglobulin G); 0 (Recombinant Proteins); 8W8T17847W (Urea)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171103
[Lr] Data última revisão:
171103
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170824
[St] Status:MEDLINE
[do] DOI:10.1002/pro.3278


  2 / 2017 MEDLINE  
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[PMID]:28623075
[Au] Autor:Sebastiao M; Quittot N; Bourgault S
[Ad] Endereço:Department of Chemistry, University of Québec in Montreal, Montreal, C.P. 8888, Succursale Centre-Ville, Montreal, H3C 3P8, Canada; Quebec Network for Research on Protein Function, Engineering, and Applications, PROTEO, Canada.
[Ti] Título:Thioflavin T fluorescence to analyse amyloid formation kinetics: Measurement frequency as a factor explaining irreproducibility.
[So] Source:Anal Biochem;532:83-86, 2017 Sep 01.
[Is] ISSN:1096-0309
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The most frequent method to monitor amyloid formation relies on the fluorescence of thioflavin T (ThT). The present study reports a novel factor of irreproducibility in ThT kinetic assays performed in microplate. Discrepancies among kinetics of amyloid assembly, performed under quiescent conditions, were associated with the frequency of fluorescence measurement. Evaluating self-assembly of the islet amyloid polypeptide at short intervals hastened its fibrillization. This observation was confirmed by transmission electron microscopy, circular dichroism spectroscopy and 8-anilino-1-naphthalenesulfonic acid fluorescence. This effect, attributed to agitation during microplate displacements between fluorescence measurements, reinforces the importance of a better standardization in amyloid formation assays.
[Mh] Termos MeSH primário: Amiloide/análise
Fluorescência
Corantes Fluorescentes/química
Polipeptídeo Amiloide das Ilhotas Pancreáticas/análise
Tiazóis/química
[Mh] Termos MeSH secundário: Amiloide/ultraestrutura
Amiloidose
Naftalenossulfonato de Anilina/química
Seres Humanos
Polipeptídeo Amiloide das Ilhotas Pancreáticas/ultraestrutura
Cinética
Microscopia Eletrônica de Transmissão
Reprodutibilidade dos Testes
Espectrometria de Fluorescência
Incerteza
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (8-anilino-1-naphthalenesulfonic acid); 0 (Amyloid); 0 (Anilino Naphthalenesulfonates); 0 (Fluorescent Dyes); 0 (Islet Amyloid Polypeptide); 0 (Thiazoles); 2390-54-7 (thioflavin T)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170912
[Lr] Data última revisão:
170912
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170618
[St] Status:MEDLINE


  3 / 2017 MEDLINE  
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[PMID]:28406291
[Au] Autor:Yu Z; Li P; Merz KM
[Ad] Endereço:Department of Chemistry, Michigan State University , East Lansing, Michigan 48824-1322, United States.
[Ti] Título:Using Ligand-Induced Protein Chemical Shift Perturbations To Determine Protein-Ligand Structures.
[So] Source:Biochemistry;56(18):2349-2362, 2017 May 09.
[Is] ISSN:1520-4995
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Protein chemical shift perturbations (CSPs), upon ligand binding, can be used to refine the structure of a protein-ligand complex by comparing experimental CSPs with calculated CSPs for any given set of structural coordinates. Herein, we describe a fast and accurate methodology that opens up new opportunities for improving the quality of protein-ligand complexes using nuclear magnetic resonance (NMR)-based approaches by focusing on the effect of the ligand on the protein. The new computational approach, H empirical chemical shift perturbation (HECSP), has been developed to rapidly calculate ligand binding-induced H CSPs in a protein. Given the dearth of experimental information by which a model could be derived, we employed high-quality density functional theory (DFT) computations using the automated fragmentation quantum mechanics/molecular mechanics approach to derive a database of ligand-induced CSPs on a series of protein-ligand complexes. Overall, the empirical HECSP model yielded correlation coefficients between its predicted and DFT-computed values of 0.897 ( HA), 0.971 ( HN), and 0.945 (side chain H) with root-mean-square errors of 0.151 ( HA), 0.199 ( HN), and 0.257 ppm (side chain H), respectively. Using the HECSP model, we developed a scoring function (NMRScore_P). We describe two applications of NMRScore_P on two complex systems and demonstrate that the method can distinguish native ligand poses from decoys and refine protein-ligand complex structures. We provide further refined models for both complexes, which satisfy the observed H CSPs in experiments. In conclusion, HECSP coupled with NMRScore_P provides an accurate and rapid platform by which protein-ligand complexes can be refined using NMR-derived information.
[Mh] Termos MeSH primário: Naftalenossulfonato de Anilina/química
Anti-Inflamatórios não Esteroides/química
Proteínas de Ligação a Ácido Graxo/química
Cetorolaco/química
Espectroscopia de Ressonância Magnética/métodos
[Mh] Termos MeSH secundário: Sítios de Ligação
Seres Humanos
Ligantes
Simulação de Acoplamento Molecular
Ligação Proteica
Conformação Proteica em alfa-Hélice
Conformação Proteica em Folha beta
Domínios Proteicos
Projetos de Pesquisa
Termodinâmica
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (8-anilino-1-naphthalenesulfonic acid); 0 (Anilino Naphthalenesulfonates); 0 (Anti-Inflammatory Agents, Non-Steroidal); 0 (Fatty Acid-Binding Proteins); 0 (Ligands); YZI5105V0L (Ketorolac)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:170615
[Lr] Data última revisão:
170615
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170414
[St] Status:MEDLINE
[do] DOI:10.1021/acs.biochem.7b00170


  4 / 2017 MEDLINE  
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[PMID]:27984146
[Au] Autor:Sohail A; Faraz M; Arif H; Bhat SA; Siddiqui AA; Bano B
[Ad] Endereço:Department of Biochemistry, Faculty of Life Sciences, AMU, Aligarh, India.
[Ti] Título:Deciphering the interaction of bovine heart cystatin with ZnO nanoparticles: Spectroscopic and thermodynamic approach.
[So] Source:Int J Biol Macromol;95:1056-1063, 2017 Feb.
[Is] ISSN:1879-0003
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:ZnO-NPs have been widely used in biomedical fields such as therapeutics, cellular imaging, and drug delivery. However, the risk of exposure of nanoparticles to the biological system is not well understood. Nanoparticle-protein interaction is pivotal to understand their biological behavior and predict nanoparticle toxicity that is crucial for its safer applications. In the present study zinc oxide nanoparticles (ZnO-NPs) were synthesized and subjected to interact with buffalo heart cystatin (BHC), purified from buffalo heart, to assess the effect(s) of ZnO-NPs on the structure and function of BHC. In vitro toxicity assessments revealed that BHC, upon interaction with ZnO-NPs, led to the altered protein conformation and perturbed function. A decrease in the anti-papain activity of BHC was observed. Spectroscopic studies demonstrated that formation of BHC-ZnO-NPs complex accompanied by structural changes in BHC along with a significant decrease in its α-helical content. ITC determined the thermodynamic parameters of binding between ZnO-NPs and BHC quantitatively. Increased surface hydrophobicity (change in the tertiary structure) was observed by ANS fluorescence that demonstrated the formation of molten globular intermediates that were found to be stable without any signs of aggregation as depicted by ThT fluorescence. TEM images gave the physical evidence of the formation of ZnO-NPs-BHC corona.
[Mh] Termos MeSH primário: Cistatinas/química
Nanopartículas/química
Óxido de Zinco/química
[Mh] Termos MeSH secundário: Naftalenossulfonato de Anilina/química
Animais
Búfalos
Cistatinas/isolamento & purificação
Interações Hidrofóbicas e Hidrofílicas
Miocárdio/química
Nanopartículas/ultraestrutura
Papaína/antagonistas & inibidores
Papaína/química
Ligação Proteica
Domínios Proteicos
Estrutura Secundária de Proteína
Espectrometria de Fluorescência
Termodinâmica
Tiazóis/química
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (8-anilino-1-naphthalenesulfonic acid); 0 (Anilino Naphthalenesulfonates); 0 (Cystatins); 0 (Thiazoles); 2390-54-7 (thioflavin T); EC 3.4.22.2 (Papain); SOI2LOH54Z (Zinc Oxide)
[Em] Mês de entrada:1704
[Cu] Atualização por classe:170406
[Lr] Data última revisão:
170406
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161217
[St] Status:MEDLINE


  5 / 2017 MEDLINE  
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[PMID]:27633281
[Au] Autor:Zhang W; Garg S; Eldi P; Zhou FH; Johnson IR; Brooks DA; Lam F; Rychkov G; Hayball J; Albrecht H
[Ad] Endereço:Centre for Pharmaceutical Innovation and Development, Centre for Drug Discovery and Development, Sansom Institute for Health Research, and School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, SA 5001, Australia.
[Ti] Título:Targeting prostate cancer cells with genetically engineered polypeptide-based micelles displaying gastrin-releasing peptide.
[So] Source:Int J Pharm;513(1-2):270-279, 2016 Nov 20.
[Is] ISSN:1873-3476
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:In recent years G protein-coupled receptors (GPCRs) have emerged as crucial tumorigenic factors that drive aberrant cancer growth, metastasis and angiogenesis. Consequently, a number of GPCRs are strongly expressed in cancer derived cell lines and tissue samples. Therefore a rational anti-cancer strategy is the design of nano-medicines that specifically target GPCRs to bind and internalise cytotoxic drugs into cancer cells. Herein, we report the genetic engineering of a self-assembling nanoparticle based on elastin-like polypeptide (ELP), which has been fused with gastrin releasing peptide (GRP). These nanoparticles increased intracellular calcium concentrations when added to GRP receptor positive PC-3 prostate cancer cells, demonstrating specific receptor activation. Moreover, GRP-displaying fluorescent labelled nanoparticles showed specific cell-surface interaction with PC-3 prostate cancer cells and increased endocytic uptake. These nanoparticles therefore provide a targeted molecular carrier system for evaluating the delivery of cytotoxic drugs into cancer cells.
[Mh] Termos MeSH primário: Portadores de Fármacos/administração & dosagem
Peptídeo Liberador de Gastrina/administração & dosagem
Micelas
Peptídeos/administração & dosagem
Proteínas Recombinantes de Fusão/administração & dosagem
[Mh] Termos MeSH secundário: Naftalenossulfonato de Anilina/química
Linhagem Celular Tumoral
Portadores de Fármacos/química
Elastina
Endocitose
Corantes Fluorescentes/química
Peptídeo Liberador de Gastrina/química
Peptídeo Liberador de Gastrina/genética
Engenharia Genética
Seres Humanos
Masculino
Peptídeos/química
Peptídeos/genética
Neoplasias da Próstata/metabolismo
Receptores da Bombesina/metabolismo
Proteínas Recombinantes de Fusão/química
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anilino Naphthalenesulfonates); 0 (Drug Carriers); 0 (Fluorescent Dyes); 0 (Micelles); 0 (Peptides); 0 (Receptors, Bombesin); 0 (Recombinant Fusion Proteins); 630I4V6051 (1-anilino-8-naphthalenesulfonate); 80043-53-4 (Gastrin-Releasing Peptide); 9007-58-3 (Elastin)
[Em] Mês de entrada:1704
[Cu] Atualização por classe:170421
[Lr] Data última revisão:
170421
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160917
[St] Status:MEDLINE


  6 / 2017 MEDLINE  
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[PMID]:27576140
[Au] Autor:Hackney DD; McGoff MS
[Ad] Endereço:Department of Biological Sciences, Carnegie Mellon University, 4400 Fifth Ave., Pittsburgh, PA, USA. Electronic address: ddh@andrew.cmu.edu.
[Ti] Título:Nucleotide-free kinesin motor domains reversibly convert to an inactive conformation with characteristics of a molten globule.
[So] Source:Arch Biochem Biophys;608:42-51, 2016 Oct 15.
[Is] ISSN:1096-0384
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Nucleotide-free kinesin motor domains from several kinesin families convert reversibly to a refractory conformation that cannot rapidly rebind ADP. In the absence of glycerol, the refractory conformation of Drosophila kinesin motor domains is favored by 50-fold with conversion of the active to the refractory species at ∼0.052 s(-1) and reactivating in the presence of ADP at ∼0.001 s(-1). This reactivation by ADP is due to conformational selection rather than induced fit because ADP is not bound to the refractory species at concentrations of ADP that are sufficient to saturate the rate of reactivation. Glycerol stabilizes the active conformation by reducing the rate of inactivation, while having little effect on the reactivation rate. Circular dichroism indicates a large conformational change occurs on formation of the refractory species. The refractory conformation binds ANS (8-anilino-1-napthalenesulfonic acid) with a large increase in fluorescence, indicating that it has molten globule character. High ANS binding is also observed with the refractory forms of Eg5 (a kinesin-5) and Ncd (a kinesin-14), indicating that a refractory conformation with molten globule characteristics may be a common feature of nucleotide-free kinesin motor domains.
[Mh] Termos MeSH primário: Drosophila melanogaster
Cinesina/química
[Mh] Termos MeSH secundário: Difosfato de Adenosina/química
Trifosfato de Adenosina/química
Naftalenossulfonato de Anilina/química
Animais
Dicroísmo Circular
Escherichia coli/metabolismo
Transferência Ressonante de Energia de Fluorescência
Glicerol/química
Concentração de Íons de Hidrogênio
Cinética
Ligação Proteica
Domínios Proteicos
Dobramento de Proteína
Espectrometria de Fluorescência
Temperatura Ambiente
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anilino Naphthalenesulfonates); 61D2G4IYVH (Adenosine Diphosphate); 8L70Q75FXE (Adenosine Triphosphate); EC 3.6.4.4 (Kinesin); PDC6A3C0OX (Glycerol)
[Em] Mês de entrada:1705
[Cu] Atualização por classe:171015
[Lr] Data última revisão:
171015
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160831
[St] Status:MEDLINE


  7 / 2017 MEDLINE  
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[PMID]:27456118
[Au] Autor:Zhang H; Wu P; Wang Y; Cao J
[Ad] Endereço:Institute of Applied Chemistry and Environmental Engineering, Yancheng Teachers University, Yancheng City, Jiangsu Province, 224002, People's Republic of China.
[Ti] Título:Affinity of miriplatin to human serum albumin and its effect on protein structure and stability.
[So] Source:Int J Biol Macromol;92:593-599, 2016 Nov.
[Is] ISSN:1879-0003
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:In this report, circular dichroism (CD) along with steady-state fluorescence spectroscopy and molecular modeling investigations were carried out to better understand the interaction of miriplatin with human serum albumin (HSA). The presence of miriplatin in solution is found to destabilize the native structure of HSA: The tertiary structure of HSA was changed and the microenvironment of Trp residue became more hydrophobic; the binding affinity of HSA with miriplatin indicating by 8-Anilino-1-naphthalenesulfonic acid (ANS) fluorescence study was 1.74×10 L/mol; miriplatin induced the denaturation and unfolding of HSA and disrupted the polar contacts and decreasing the reversibility of the unfolding process of protein. In addition, molecular modeling studies indicated miriplatin bound to domain II of HSA by hydrophobic force, hydrogen bonds, and electrostatic force interactions. HSA retained most of its esterase activity even after its binding with miriplatin. These results provide valuable insight into the binding mechanism between miriplatin and a plasma protein that is known to play an important role in the drug delivery of medicinal drugs to target organs.
[Mh] Termos MeSH primário: Compostos Organoplatínicos/metabolismo
Albumina Sérica/química
Albumina Sérica/metabolismo
[Mh] Termos MeSH secundário: Naftalenossulfonato de Anilina/química
Sítios de Ligação
Dicroísmo Circular
Esterases/metabolismo
Seres Humanos
Simulação de Acoplamento Molecular
Compostos Organoplatínicos/química
Compostos Organoplatínicos/farmacologia
Desnaturação Proteica/efeitos dos fármacos
Estabilidade Proteica/efeitos dos fármacos
Estrutura Secundária de Proteína
Espectrometria de Fluorescência
Temperatura Ambiente
Triptofano/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (8-anilino-1-naphthalenesulfonic acid); 0 (Anilino Naphthalenesulfonates); 0 (Organoplatinum Compounds); 0 (Serum Albumin); 780F0P8N4I (miriplatin); 8DUH1N11BX (Tryptophan); EC 3.1.- (Esterases)
[Em] Mês de entrada:1703
[Cu] Atualização por classe:170313
[Lr] Data última revisão:
170313
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160727
[St] Status:MEDLINE


  8 / 2017 MEDLINE  
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[PMID]:27191938
[Au] Autor:Lohrasbi-Nejad A; Torkzadeh-Mahani M; Hosseinkhani S
[Ad] Endereço:Department of Biochemistry, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran.
[Ti] Título:Hydrophobin-1 promotes thermostability of firefly luciferase.
[So] Source:FEBS J;283(13):2494-507, 2016 Jul.
[Is] ISSN:1742-4658
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:The thermal sensitivity of firefly luciferase limits its use in certain applications. Firefly luciferase has hydrophobic sites on its surface, which lead to aggregation and inactivation of the enzyme at temperatures over 30 °C. We have successfully stabilized firefly luciferase at high temperatures with the assistance of a unique protein, hydrophobin-1 (HFB1). HFB1 is a small secretory protein belonging to class II of hydrophobins with a low molecular weight (7.5 kDa) and distinct functional hydrophobic patch on its surface. The interaction of HFB1 with hydrophobic sites on the surface of luciferase was confirmed by extrinsic fluorescence studies using 8-anilino-1-naphthalenesulfonic acid (ANS) as a hydrophobic reporter probe. Calculation of thermodynamic parameters of heat inactivation of luciferase shows that conformational changes and flexibility of enzyme decreased in the presence of HFB1, and thermostability of the HFB1-treated enzyme increased. Furthermore, the addition of HFB1 into the enzymatic solution leads to an increase in catalytic efficiency of luciferase and subsequently improves the utility of the enzyme as an ATP detector.
[Mh] Termos MeSH primário: Luciferases de Vaga-Lume/química
Luciferases de Vaga-Lume/metabolismo
[Mh] Termos MeSH secundário: Naftalenossulfonato de Anilina/química
Animais
Bovinos
Estabilidade Enzimática
Temperatura Alta
Interações Hidrofóbicas e Hidrofílicas
Cinética
Medições Luminescentes
Soroalbumina Bovina/química
Soroalbumina Bovina/metabolismo
Temperatura Ambiente
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (8-anilino-1-naphthalenesulfonic acid); 0 (Anilino Naphthalenesulfonates); 27432CM55Q (Serum Albumin, Bovine); EC 1.13.12.7 (Luciferases, Firefly)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160519
[St] Status:MEDLINE
[do] DOI:10.1111/febs.13757


  9 / 2017 MEDLINE  
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[PMID]:27025561
[Au] Autor:Rani A; Jayaraj A; Jayaram B; Pannuru V
[Ad] Endereço:Department of Chemistry, University of Delhi, Delhi-110 007, India.
[Ti] Título:Trimethylamine-N-oxide switches from stabilizing nature: A mechanistic outlook through experimental techniques and molecular dynamics simulation.
[So] Source:Sci Rep;6:23656, 2016 Mar 30.
[Is] ISSN:2045-2322
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:In adaptation biology of the discovery of the intracellular osmolytes, the osmolytes are found to play a central role in cellular homeostasis and stress response. A number of models using these molecules are now poised to address a wide range of problems in biology. Here, a combination of biophysical measurements and molecular dynamics (MD) simulation method is used to examine the effect of trimethylamine-N-oxide (TMAO) on stem bromelain (BM) structure, stability and function. From the analysis of our results, we found that TMAO destabilizes BM hydrophobic pockets and active site as a result of concerted polar and non-polar interactions which is strongly evidenced by MD simulation carried out for 250 ns. This destabilization is enthalpically favourable at higher concentrations of TMAO while entropically unfavourable. However, to the best of our knowledge, the results constitute first detailed unambiguous proof of destabilizing effect of most commonly addressed TMAO on the interactions governing stability of BM and present plausible mechanism of protein unfolding by TMAO.
[Mh] Termos MeSH primário: Metilaminas/química
[Mh] Termos MeSH secundário: Naftalenossulfonato de Anilina/química
Bromelaínas/química
Domínio Catalítico
Dicroísmo Circular
Estabilidade Enzimática
Ligações de Hidrogênio
Interações Hidrofóbicas e Hidrofílicas
Simulação de Dinâmica Molecular
Ligação Proteica
Conformação Proteica em alfa-Hélice
Desdobramento de Proteína
Proteólise
Espectroscopia de Infravermelho com Transformada de Fourier
Termodinâmica
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Anilino Naphthalenesulfonates); 0 (Methylamines); 9001-00-7 (Bromelains); FLD0K1SJ1A (trimethyloxamine)
[Em] Mês de entrada:1702
[Cu] Atualização por classe:170220
[Lr] Data última revisão:
170220
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160331
[St] Status:MEDLINE
[do] DOI:10.1038/srep23656


  10 / 2017 MEDLINE  
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[PMID]:27000059
[Au] Autor:Xu Y; Lee J; Lü ZR; Mu H; Zhang Q; Park YD
[Ad] Endereço:Zhejiang Provincial Key Laboratory of Applied Enzymology, Yangtze Delta Region Institute of Tsinghua University, Jiaxing, 314006, People's Republic of China.
[Ti] Título:Integration of Inhibition Kinetics and Molecular Dynamics Simulations: A Urea-Mediated Folding Study on Acetaldehyde Dehydrogenase 1.
[So] Source:Appl Biochem Biotechnol;179(6):1101-14, 2016 Jul.
[Is] ISSN:1559-0291
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Understanding the mechanism of acetaldehyde dehydrogenase 1 (ALDH1) folding is important because this enzyme is directly involved in several types of cancers and other diseases. We investigated the urea-mediated unfolding of ALDH1 by integrating kinetic inhibition studies with computational molecular dynamics (MD) simulations. Conformational changes in the enzyme structure were also analyzed using intrinsic and 1-anilinonaphthalene-8-sulfonate (ANS)-binding fluorescence measurements. Kinetic studies revealed that the direct binding of urea to ALDH1 induces inactivation of ALDH1 in a manner of mixed-type inhibition. Tertiary structural changes associated with regional hydrophobic exposure of the active site were observed. The urea binding regions on ALDH1 were predicted by docking simulations and were partly shared with active site residues of ALDH1 and with interface residues of the oligomerization domain for tetramer formation. The docking results suggest that urea prevents formation of the ALDH1 normal shape for the tetramer state as well as entrance of the substrate into the active site. Our study provides insight into the structural changes that accompany urea-mediated unfolding of ALDH1 and the catalytic role associated with conformational changes.
[Mh] Termos MeSH primário: Isoenzimas/química
Conformação Proteica
Dobramento de Proteína
Retinal Desidrogenase/química
Ureia/química
[Mh] Termos MeSH secundário: Naftalenossulfonato de Anilina/química
Sítios de Ligação
Domínio Catalítico
Seres Humanos
Isoenzimas/antagonistas & inibidores
Isoenzimas/metabolismo
Cinética
Simulação de Dinâmica Molecular
Retinal Desidrogenase/antagonistas & inibidores
Retinal Desidrogenase/metabolismo
Espectrometria de Fluorescência
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (8-anilino-1-naphthalenesulfonic acid); 0 (Anilino Naphthalenesulfonates); 0 (Isoenzymes); 8W8T17847W (Urea); EC 1.2.1.- (aldehyde dehydrogenase 1); EC 1.2.1.36 (Retinal Dehydrogenase)
[Em] Mês de entrada:1701
[Cu] Atualização por classe:170113
[Lr] Data última revisão:
170113
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160323
[St] Status:MEDLINE
[do] DOI:10.1007/s12010-016-2052-5



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