A5007865038- RNA and protein synthesis mechanisms
- DNA and Nucleic Acid Chemistry
- Viral Infections and Immunology Research
- Hepatitis C virus research
- RNA modifications and cancer
- RNA Research and Splicing
- HIV Research and Treatment
- HIV/AIDS drug development and treatment
- Advanced biosensing and bioanalysis techniques
- RNA regulation and disease
- Bacteriophages and microbial interactions
- RNA Interference and Gene Delivery
- Metal complexes synthesis and properties
- Click Chemistry and Applications
- Cancer therapeutics and mechanisms
- Educational Research and Science Teaching
- Enzyme Structure and Function
- Antibiotic Resistance in Bacteria
- Biochemical and biochemical processes
- Viral gastroenteritis research and epidemiology
- Chemical Synthesis and Analysis
- Organizational Management and Innovation
- E-Learning and Knowledge Management
- SARS-CoV-2 and COVID-19 Research
- Infectious Encephalopathies and Encephalitis
Valencia Catholic University Saint Vincent Martyr
2015-2024
Universidad de Alcalá
1993-2023
Software (Spain)
2023
Robert Bosch (Germany)
2022
Universitat de València
2013-2021
Centro Nacional de Microbiologia
2013
Instituto de Salud Carlos III
2013
Centro de Investigacion Principe Felipe
2007-2011
MRC Laboratory of Molecular Biology
2001-2009
Stanford University
2009
Abstract The current pandemic situation caused by the Betacoronavirus SARS-CoV-2 (SCoV2) highlights need for coordinated research to combat COVID-19. A particularly important aspect is development of medication. In addition viral proteins, structured RNA elements represent a potent alternative as drug targets. search drugs that target requires their high-resolution structural characterization. Using nuclear magnetic resonance (NMR) spectroscopy, worldwide consortium NMR researchers aims...
Hydrophobic base analogues (HBAs) have shown great promise for the expansion of chemical and coding potential nucleic acids but are generally poor polymerase substrates. While extensive synthetic efforts yielded examples HBAs with favorable substrate properties, their discovery has remained challenging. Here we describe a complementary strategy improving HBA properties by directed evolution dedicated using compartmentalized self-replication (CSR) archetypal 5-nitroindole (d5NI) its...
Loop–loop tertiary interactions play a key role in the folding and catalytic activity of natural hammerhead ribozymes. Using combination NMR spectroscopy, site-directed mutagenesis kinetic infectivity analyses, we have examined structure function loops 1 2 (+) (–) hammerheads chrysanthemum chlorotic mottle viroid RNA. In both hammerheads, loop is heptanucleotide hairpin containing an exposed U at its 5′ side extrahelical 3′-side critical for ribozyme vitro vivo , whereas has opened A...
Transmissible gastroenteritis coronavirus (TGEV) genomic RNA transcription generates 5'- and 3'-coterminal subgenomic mRNAs. This process involves a discontinuous step during the synthesis of minus-sense that is modulated by transcription-regulating sequences located at 3' end leader (TRS-L) also preceding each viral gene (TRS-Bs). TRSs include highly conserved core sequence (CS) (5'-CUAAAC-3') variable flanking sequences. It has been previously proposed TRS-Bs act as attenuation or stop...
Using a combination of nuclear magnetic resonance (NMR) spectroscopy experiments and molecular dynamics, we have analyzed the structure dynamics complex between bisnaphthalimide drug LU-79553 DNA duplex d(ATGCAT)2. is DNA-binding topoisomerase II inhibitor that particularly effective against human solid tumors are refractory to other drugs. We found two naphthalimide chromophores bisintercalate at TpG CpA steps hexanucleotide, stacking mainly with purine G A bases from opposite strands. The...
The 3′X domain is a 98-nt region located at the 3′ end of hepatitis C virus genomic RNA that plays essential functions in viral life cycle. It contains an absolutely conserved, 16-base palindromic sequence promotes dimerization, overlapped with 7-nt tract implicated distal contact nearby functional sequence. Using small angle X-ray scattering measurements combined model building guided by NMR spectroscopy, we have studied stoichiometry, structure, and flexibility two smaller subdomain...
Abstract Subdomain 5BSL3.2 of hepatitis C virus RNA lies at the core a network distal RNA–RNA contacts that connect 5′ and 3′ regions viral genome regulate translation replication stages cycle. Using small-angle X-ray scattering NMR spectroscopy experiments, we have determined low resolution structural models this subdomain its complex with domain 3′X, located 3′-terminus chain. adopts characteristic ‘L’ shape in solution, whereas 5BSL3.2–3′X forms highly unusual ‘Y’-shaped kissing junction...
The leader RNA sequence of human immunodeficiency virus type 1 (HIV-1) consists a complex series stem loop structures that are critical for viral replication. Three-dimensional structural analysis by NMR one these structures, the SL1 packaging signal region, revealed highly conserved purine rich with structure nearly identical to Rev-binding Rev response element. Using band-shift assays, surface plasmon resonance, and further analysis, we demonstrate this binds Rev. HIV-1 appears have second...
NAG (N-acetyl-L-glutamate), the essential allosteric activator of first urea cycle enzyme, CPSI (carbamoyl phosphate synthetase I), is a key regulator this crucial for ammonia detoxification in animals (including humans). Automated cavity searching and flexible docking have allowed identification site crystal structure human C-terminal domain. The site, pocket lined by invariant residues located between central beta-sheet two alpha-helices, opens at C-edge roofed three-residue lid. It can...
The sequence-specific structural and dynamic properties of double-helical DNA play important roles in many biological processes involving recognition. Using a combination NMR spectroscopy, surface plasmon resonance, UV thermal denaturation experiments, we have investigated how sequences not making direct contact with the drug modulate interaction between cytotoxic agent elinafide its preferred bisintercalation sites on DNA. Our combined data are consistent two superposed interactions, one...
RNA-bindende Inhibitoren mit einem bilateral substituierten p-Terphenylengerüst (grün) projizieren ihre Substituenten in breiten Winkelbereich und reproduzieren die Wechselwirkungen einer ihren RNA-Rezeptor eingebetteten Protein-α-Helix (rot). Diese Terphenyle können eine α-Helix des HIV-1-Proteins Rev nachahmen inhibieren Funktion von sowie Replikation HIV-1 Zellen.