A5101759164- RNA and protein synthesis mechanisms
- RNA modifications and cancer
- Viral Infections and Immunology Research
- DNA and Nucleic Acid Chemistry
- Hepatitis C virus research
- Bacterial Genetics and Biotechnology
- Advanced biosensing and bioanalysis techniques
- Bacteriophages and microbial interactions
- Biochemical and Molecular Research
- X-ray Diffraction in Crystallography
- Crystallization and Solubility Studies
- Enzyme Structure and Function
- RNA Research and Splicing
- Chemical Synthesis and Analysis
- Antimicrobial Peptides and Activities
- RNA Interference and Gene Delivery
- Synthesis and Biological Evaluation
- HIV/AIDS drug development and treatment
- Synthesis and Catalytic Reactions
- Click Chemistry and Applications
- Asymmetric Synthesis and Catalysis
- Crystallography and molecular interactions
- Cancer, Hypoxia, and Metabolism
- HIV Research and Treatment
- Synthesis of β-Lactam Compounds
University of California, San Diego
2012-2023
Center for Discovery
2017-2020
Weatherford College
2020
La Jolla Alcohol Research
2015
Memorial Sloan Kettering Cancer Center
1999-2011
Kettering University
2000
Cornell University
2000
Institut de Biologie Moléculaire et Cellulaire
1999
Centre National de la Recherche Scientifique
1997
Max Planck Institute of Experimental Medicine
1997
We report the results of a first, collective, blind experiment in RNA three-dimensional (3D) structure prediction, encompassing three prediction puzzles. The goals are to assess leading edge techniques; compare existing methods and tools; evaluate their relative strengths, weaknesses, limitations terms sequence length structural complexity. should give potential users insight into suitability available for different applications facilitate efforts community ongoing improve tools. also...
The three-dimensional structures of noncoding RNA molecules reveal recurring architectural motifs that have been exploited for the design artificial nanomaterials. Programmed assembly nanoobjects from autonomously folding tetraloop-receptor complexes as well junction has achieved previously through sequence-directed hybridization complex sets long oligonucleotides. Due to size and complexity, structural characterization limited low-resolution microscopy studies. Here we present design,...
In many steps of gene replication and expression, RNA molecules participate as key players, which renders them attractive targets for therapeutic intervention. While the function nucleic acids carriers genetic material is based on their sequence, a number important RNAs are involved in processes that depend defined three-dimensional structures these molecules. As proteins, numerous complex folds exist. The development drugs bind specifically to opens exciting new ways expand greatly existing...
Adenine flips out: A combination of X-ray crystallography, 2-aminopurine fluorescence labeling, and the use aminoglycosides as ligands is exploited to demonstrate conformational transitions in RNA domain that ensures accurate protein synthesis (see picture). The triggering a change an adenine unit by ligand binding can be used basis screening method discover antibiotics. Supporting information for this article available on WWW under http://www.wiley-vch.de/contents/jc_2002/2004/z54217_s.pdf...
The internal ribosome entry site (IRES) in the hepatitis C virus (HCV) RNA genome is essential for initiation of viral protein synthesis. IRES domains adopt well-defined folds that are potential targets antiviral translation inhibitors. We have determined three-dimensional structure subdomain IIa complex with a benzimidazole inhibitor at 2.2 Å resolution. Comparison to unbound conjunction studies binding target solution demonstrate undergoes dramatic ligand-induced conformational adaptation...
Nanopores are single-molecule sensors that show exceptional promise as a biomolecular analysis tool by enabling label-free detection of small amounts sample. In this paper, we demonstrate nanopores capable detecting the conformation an antiviral RNA drug target. The hepatitis C virus uses internal ribosome entry site (IRES) motif in order to initiate translation docking ribosomes its host cell. IRES is therefore viable and important Drug-induced changes HCV motif, from bent straight...
The lack of high RNA target selectivity displayed by aminoglycoside antibiotics results from both their electrostatically driven binding mode and conformational adaptability. inherent flexibility around glycosidic bonds allows them to easily assume a variety conformations, permitting structurally adapt diverse targets. This structural promiscuity in the formation complexes with targets which distinct conformations. Such differences suggest that covalently linking individual rings an could...
DNA and RNA have emerged as a material for nanotechnology applications that take advantage of the nucleic acids' ability to encode folding programmable self-assembly through mainly base pairing. The two types acid rarely been used in combination enhance structural diversity or partitioning functional architectural roles. Here, we report design screening strategy integrate combinations motifs joints building blocks modules versatile toolkit polygonal nanoshapes. Clean incorporation diverse...
Retroviruses encapsidate their genome as a dimer of homologous RNA molecules noncovalently linked close to 5′ ends. The dimerization initiation site (DIS) human immunodeficiency virus type 1 (HIV-1) is hairpin structure that contains in the loop 6-nt self-complementary sequence flanked by two and one 3′ purines. sequence, well flanking purines, are crucial for HIV-1 RNA, which mediated formation "kissing-loop" complex between DIS each monomer. Here, we used chemical modification...
The preorganized presentation of functional groups in the antibiotic neomycin (green) is exploited to obtain a conformationally restricted aminoglycoside (yellow) by regioselective intramolecular cyclization. X-ray crystallography data show how natural product and derivative recognize RNA target motif that binding site antibiotics.
An internal ribosome entry site (IRES) initiates protein synthesis in RNA viruses, including the hepatitis C virus (HCV). We have discovered ligand-responsive conformational switches viral IRES elements. Modular motifs of greatly distinct sequence and local secondary structure been found to serve as functionally conserved involved IRES-driven translation may be captured by identical cognate ligands. The described here constitute a new paradigm for ligand-captured that differ from...
Abstract RNA nanotechnology uses structural motifs to build nanosized architectures that assemble through selective base‐pair interactions. Herein, we report the crystal‐structure‐guided design of highly stable nanotriangles self‐assemble cooperatively from short oligonucleotides. The crystal structure an 81 nucleotide nanotriangle determined at 2.6 Å resolution reveals so‐far smallest circularly closed nanoobject made entirely double‐stranded RNA. assembly architecture involved corner were...
In the groove: The crystal structure of bacterial decoding-site RNA in a complex with antibiotic apramycin reveals how glycoside scaffolds participate recognition by natural products through formation pseudo base pairs and triples. suggests that inhibitory action is based on interaction ribosomal protein S12 (see structural model), control element ribosome translocation. Supporting Information for this article available WWW under http://www.wiley-vch.de/contents/jc_2002/2005/z500028_s.pdf or...
Around the bend: A right-angled bend in RNA of hepatitis C virus is stabilized by a core divalent metal ions (shown as green and violet spheres). Crystal-structure analysis fluorescence labeling have been used to investigate structure metal-ion-dependent stabilization domain that plays key role viral protein synthesis. Supporting information for this article available on WWW under http://www.wiley-vch.de/contents/jc_2002/2007/z603807_s.pdf or from author. Please note: The publisher not...