A5050005304- Heat shock proteins research
- Peroxisome Proliferator-Activated Receptors
- X-ray Diffraction in Crystallography
- Crystallization and Solubility Studies
- Research on Leishmaniasis Studies
- RNA Research and Splicing
- thermodynamics and calorimetric analyses
- Cancer, Hypoxia, and Metabolism
- Adipose Tissue and Metabolism
- Computational Drug Discovery Methods
- RNA and protein synthesis mechanisms
- Metabolism, Diabetes, and Cancer
- Trypanosoma species research and implications
- Protein Structure and Dynamics
- Transgenic Plants and Applications
- Adipokines, Inflammation, and Metabolic Diseases
- Pneumocystis jirovecii pneumonia detection and treatment
- Herbal Medicine Research Studies
- Protein Degradation and Inhibitors
- Retinoids in leukemia and cellular processes
- Biochemical and Molecular Research
- Bacteriophages and microbial interactions
- Tea Polyphenols and Effects
- Genetics and Neurodevelopmental Disorders
- Genomics and Chromatin Dynamics
Brazilian Biosciences National Laboratory
2017-2024
Instituto Dante Pazzanese de Cardiologia
2024
Brazilian Center for Research in Energy and Materials
2017-2024
Laboratório Nacional de Ciência e Tecnologia do Bioetanol
2018-2021
Universidade de São Paulo
2009-2020
Universidade Federal de São Carlos
2010-2018
Universidade Estadual de Campinas (UNICAMP)
2009
Universidade Federal do Rio de Janeiro
2009
The nucleocapsid (N) protein of the SARS-CoV-2 virus, causal agent COVID-19, is a multifunction phosphoprotein that plays critical roles in virus life cycle, including transcription and packaging viral RNA. To play such diverse roles, N has two globular RNA-binding modules, N- (NTD) C-terminal (CTD) domains, which are connected by an intrinsically disordered region. Despite wealth structural data available for isolated NTD CTD, how these domains arranged full-length oligomerization...
BACKGROUND AND OBJECTIVE: To determine factors causing inflammation after intravitreal aflibercept injections. PATIENTS METHODS: This case-control study included aflibercept-treated eyes with post-injection and control eyes. Medical records were analyzed to identify contributing factors. Biophysical tests performed characterize properties of particle aggregation. Institutional review board approval was obtained. RESULTS: Inflammation developed in six eyes; three patients had anterior...
Peroxisome proliferator activated receptors (PPARs δ, α and γ) are closely related transcription factors that exert distinct effects on fatty acid glucose metabolism, cardiac disease, inflammatory response other processes. Several groups developed PPAR subtype specific modulators to trigger desirable of particular PPARs without harmful side associated with activation subtypes. Presently, however, many compounds bind one the cross-react others rational strategies obtain highly selective far...
Current studies estimate that 1–3% of females with unexplained intellectual disability (ID) present de novo splice site, nonsense, frameshift, or missense mutations in the DDX3X protein (DEAD-Box Helicase 3 X-Linked). However, cellular and molecular mechanisms by which impair brain development are not fully comprehended. Here, we show ID-linked mutation L556S renders prone to aggregation. By using a combination biophysical assays imaging approaches, demonstrate this mutant assembles...
Abstract The nucleocapsid (N) protein plays critical roles in coronavirus genome transcription and packaging, representing a key target for the development of novel antivirals, which structural information on ligand binding is scarce. We used fluorescence polarization assay to identify small molecules that disrupt N RNA derived from SARS-CoV-2 packaging signal. Several phenolic compounds, including L-chicoric acid (CA), were identified as high-affinity N-protein ligands. CA was confirmed by...
The peroxisome proliferator-activated receptors (PPARs) regulate genes involved in lipid and carbohydrate metabolism, are targets of drugs approved for human use. Whereas the crystallographic structure complex full length PPARγ RXRα is known, structural alterations induced by heterodimer formation DNA contacts not well understood. Herein, we report a small-angle X-ray scattering analysis oligomeric state hPPARγ alone presence retinoid X receptor (RXR). results reveal that, contrast with...
Peroxisome proliferator-activated receptor gamma (PPARγ) is a member of nuclear superfamily and acts as ligand-dependent transcription factor, playing key roles in maintenance adipose tissue regulation glucose lipid homeostasis. This the target thiazolidinediones, class antidiabetic drugs, that improve insulin sensitization regulate glycemia type 2 diabetes. Despite beneficial effects such rosiglitazone pioglitazone, their use associated with several side effects, including weight gain,...
The small acidic protein called p23 acts as a co-chaperone for heat-shock of 90 kDa (Hsp90) during its ATPase cycle. proteins inhibit Hsp90 activity and show intrinsic chaperone activity. A search in protozoa, especially trypanosomatids, led us to identify two putative the Leishmania braziliensis genome that share approximately 30% identity with each other human p23. To understand presence isoforms we obtained recombinant L. (named Lbp23A Lbp23B) performed structural functional studies....
Peroxisome proliferator-activated receptor gamma (PPARγ) is a nuclear with key role in metabolic processes and target of CDK5 kinase phosphorylation at S245 (S273 PPARγ isoform 2), thereby inducing insulin resistance. A remarkable effort has been addressed to find ligands that inhibit phosphorylation, but the poor understanding this field challenges design such ligands. Here, through computational biophysical methods, we explored an experimentally validated model PPARγ-CDK5 complex,...
Abstract Thirteen new reblastatin derivatives, with alkynyl, amino and fluoro substituents on the aromatic ring, were prepared by a chemo‐biosynthetic approach using an AHBA(−) mutant strain of Streptomyces hygroscopicus , geldanamycin producer. The inhibitory potencies these mutaproducts extended library natural products derivatives probed purified heat shock proteins (Hsps), obtained from Leishmania braziliensis (LbHsp90) as well human sources (HsHsp90). We determined activities potential...
Leishmaniasis is a neglected disease caused by the protozoa Leishmania ssp. Environmental differences found parasites in vector and host are translated into cellular stress, leading to production of heat shock proteins (Hsp). These molecular chaperones involved folding nascent as well regulation gene expression, signalling events proteostasis. Since spp. use Hsp90 trigger important transitions between their different stages life cycle, this protein family becomes profitable target...
3D skin models have been explored as an alternative method to the use of animals in research and development. Usually, human equivalents comprise only epidermis or epidermis/dermis layers. Herein, we leverage bioprinting technology fabricate a full-thickness equivalent with hypodermis (HSEH). The collagen hydrogel-based structure provides mimetic environment for cells adhere, proliferate differentiate. effective incorporation layer is evidenced by scanning electron microscopy,...
The glutaminase (GLS) enzyme hydrolyzes glutamine into glutamate, an important anaplerotic source for the tricarboxylic acid cycle in rapidly growing cancer cells under Warburg effect. Glutamine-derived α-ketoglutarate is also cofactor of chromatin-modifying enzymes, and through epigenetic changes, it keeps undifferentiated state. Moreover, glutamate neurotransmitter, deregulated activity nervous system underlies several neurological disorders. Given proven importance critical diseases, we...
The activity of Thioredoxin-1 (Trx-1) is adjusted by the balance its monomeric, active and dimeric, inactive state. regulation this not completely understood. We have previously shown that cytoplasmic domain transmembrane protein A Disintegrin And Metalloprotease 17 (ADAM17cyto) binds to destabilization interaction favors dimeric state Trx-1. Here, we investigate whether ADAM17 plays a role in conformation activation found disrupting interacting interface with Trx-1 site-directed mutagenesis...
The nuclear receptor PPARγ is essential to maintain whole-body glucose homeostasis and insulin sensitivity, acting as a master regulator of adipogenesis, lipid, metabolism. Its activation through natural or synthetic ligands induces the recruitment coactivators, leading transcription target genes such cytokines hormones. More recently, post translational modifications, phosphorylation at Ser273 by CDK5 in adipose tissue, have been linked resistance trough dysregulation expression specific...
The ligand binding domain (LBD) of nuclear hormone receptors adopts a very compact, mostly alpha-helical structure that binds specific ligands with high affinity. We use circular dichroism spectroscopy and high-temperature molecular dynamics simulations to investigate unfolding the LBDs thyroid (TRs). A description denaturation mechanisms is obtained by TRalpha TRbeta in absence presence natural Triac. show thermal LBD starts loss native contacts secondary elements, while remains essentially...
MAF1 is a phosphoprotein that plays critical role in cell growth control as the central regulator of RNA polymerase (Pol) III activity. Citrus (CsMAF1) was identified direct target PthA4, bacterial effector protein required to induce tumors citrus. CsMAF1 binds Pol restrict transcription; however, exactly how interacts with and phosphorylation modulates this interaction unknown. Moreover, PthA4 also obscure. Here we show predominantly WH1 domain citrus subunit C34 (CsC34) its...