A5091692002- thermodynamics and calorimetric analyses
- Protein Structure and Dynamics
- Enzyme Structure and Function
- Computational Drug Discovery Methods
- RNA and protein synthesis mechanisms
- RNA modifications and cancer
- HIV/AIDS drug development and treatment
- Photosynthetic Processes and Mechanisms
- ATP Synthase and ATPases Research
- Lipid Membrane Structure and Behavior
- Helicobacter pylori-related gastroenterology studies
- Heat shock proteins research
- Mitochondrial Function and Pathology
- Biochemical and Molecular Research
- HIV Research and Treatment
- Monoclonal and Polyclonal Antibodies Research
- Veterinary medicine and infectious diseases
- Crystallization and Solubility Studies
- Genetics and Neurodevelopmental Disorders
- RNA Research and Splicing
- Genomics and Chromatin Dynamics
- Protein Kinase Regulation and GTPase Signaling
- RNA Interference and Gene Delivery
- X-ray Diffraction in Crystallography
- Metal-Catalyzed Oxygenation Mechanisms
Universidad de Zaragoza
2016-2025
Instituto de Investigación Sanitaria Aragón
2016-2025
Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas
2017-2025
Centre for Biomedical Network Research on Rare Diseases
2017-2025
Centro de Investigación Biomédica en Red
2010-2025
Instituto de Biocomputación y Física de Sistemas Complejos
2013-2024
Instituto de Salud Carlos III
2017-2024
Research Center Borstel - Leibniz Lung Center
2024
Real Academia Española
2018-2023
Josep Carreras Leukaemia Research Institute
2023
SARS (severe acute respiratory syndrome) is caused by a newly discovered coronavirus. A key enzyme for the maturation of this virus and, therefore, target drug development main protease 3CLpro (also termed SARS-CoV 3CLpro). We have cloned and expressed in Escherichia coli full-length as well truncated form containing only catalytic domains. The recombinant proteins been characterized enzymatically using fluorescently labeled substrate; their structural stability solution has determined...
Phenylketonuria (PKU) is an inborn error of metabolism caused by mutations in phenylalanine hydroxylase (PAH). Over 500 disease-causing have been identified humans, most which result PAH protein misfolding and increased turnover vivo. The use pharmacological chaperones to stabilize or promote correct folding mutant proteins represents a promising new direction the treatment diseases. We performed high-throughput ligand screen over 1,000 agents 4 compounds (I–IV) that enhanced thermal...
Abstract Transthyretin (TTR) is a plasma homotetrameric protein implicated in fatal systemic amyloidoses. TTR tetramer dissociation precedes pathological aggregation. Native state stabilizers are promising drugs to treat Here we repurpose tolcapone, an FDA-approved molecule for Parkinson’s disease, as potent aggregation inhibitor. Tolcapone binds specifically human plasma, stabilizes the native vivo mice and humans inhibits cytotoxicity. Crystal structures of tolcapone bound wild-type V122I...
Abstract Apoptosis is a highly regulated form of programmed cell death, essential to the development and homeostasis multicellular organisms. Cytochrome c central figure in activation apoptotic intrinsic pathway, thereby activating caspase cascade through its interaction with Apaf-1. Our recent studies have revealed 14-3-3ε (a direct inhibitor Apaf-1) as cytosolic cytochrome target. Here we explore / show ability block 14-3-3ε-mediated Apaf-1 inhibition, unveiling novel function for an...
Intrinsically disordered proteins (IDPs) are prevalent in eukaryotes, performing signaling and regulatory functions. Often associated with human diseases, they constitute drug-development targets. NUPR1 is a multifunctional IDP, over-expressed involved pancreatic ductal adenocarcinoma (PDAC) development. By screening 1120 FDA-approved compounds, fifteen candidates were selected, their interactions characterized by experimental simulation techniques. The protein remained upon binding to all...
Intrinsically disordered proteins (IDPs) are emerging as attractive drug targets by virtue of their prevalence in various diseases including cancer. Drug development targeting IDPs is challenging because they have dynamical structure features and conventional design not applicable. NUPR1 an IDP playing important role pancreatic We previously reported that Trifluoperazine (TFP), antipsychotic agent, was capable binding to inhibiting tumors growth. Unfortunately, TFP showed strong central...
The pandemic, due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has stimulated the search for antivirals tackle COVID-19 infection. Molecules with known pharmacokinetics and already approved human use have been demonstrated or predicted be suitable used either directly as a base scaffold-based drug design. Among these substances, quercetin is potent in vitro inhibitor of 3CLpro, SARS-CoV-2 main protease. However, its low vivo bioavailability calls modifications molecular...
The development of new antiviral drugs against SARS-CoV-2 is a valuable long-term strategy to protect the global population from COVID-19 pandemic complementary vaccination. Considering this, viral main protease (Mpro) among most promising molecular targets in light its importance during replication cycle. natural flavonoid quercetin 1 has been recently reported be potent Mpro inhibitor vitro, and we explored effect produced by introduction organoselenium functionalities this scaffold. In...
The vast majority of HIV-1 infections in Africa are caused by the A and C viral subtypes rather than B subtype prevalent United States Western Europe. Genomic differences between give rise to sequence variations encoded proteins, including protease. Because some amino acid polymorphisms occur at sites that have been associated with drug resistance subtype, it is important assess effectiveness protease inhibitors developed against different subtypes. Here we report enzymatic characterization...
The wobble uridine of certain bacterial and mitochondrial tRNAs is modified, at position 5, through an unknown reaction pathway that utilizes the evolutionarily conserved MnmE GidA proteins. resulting modification (a methyluridine derivative) plays a critical role in decoding NNG/A codons reading frame maintenance during mRNA translation. lack this tRNA produces pleiotropic phenotype bacteria has been associated with encephalomyopathies humans. In work, we use vitro vivo approaches to...
Since the first description of apoptosis four decades ago, great efforts have been made to elucidate, both in vivo and vitro, molecular mechanisms involved its regulation. Although role cytochrome c during is well established, relatively little known about participation signaling pathways due essential respiration. To obtain a better understanding onset apoptosis, we used proteomic approach based on affinity chromatography with as bait this study. In approach, novel interaction partners were...
Abstract Inosine-5′-monophosphate dehydrogenase (IMPDH) plays key roles in purine nucleotide metabolism and cell proliferation. Although IMPDH is a widely studied therapeutic target, there limited information about its physiological regulation. Using Ashbya gossypii as model, we describe the molecular mechanism structural basis for allosteric regulation of by guanine nucleotides. We report that GTP GDP bind to regulatory Bateman domain, inducing octamers with compromised catalytic activity....