A5067811184- Enzyme Structure and Function
- Biochemical and Molecular Research
- Protein Structure and Dynamics
- Machine Learning in Bioinformatics
- Bacteriophages and microbial interactions
- Antibiotic Resistance in Bacteria
- Microbial Community Ecology and Physiology
- Glycosylation and Glycoproteins Research
- Carbohydrate Chemistry and Synthesis
- Enzyme Production and Characterization
- Genomics and Phylogenetic Studies
- RNA and protein synthesis mechanisms
- Photosynthetic Processes and Mechanisms
- Nitric Oxide and Endothelin Effects
- Neuroscience and Neuropharmacology Research
- Neurogenesis and neuroplasticity mechanisms
- Peroxisome Proliferator-Activated Receptors
- Mitochondrial Function and Pathology
- Inorganic Fluorides and Related Compounds
- Cancer Research and Treatments
- Microtubule and mitosis dynamics
- Antibiotics Pharmacokinetics and Efficacy
- Adipose Tissue and Metabolism
- Axon Guidance and Neuronal Signaling
- Pharmaceutical and Antibiotic Environmental Impacts
University of California, San Francisco
2021-2023
Rice University
2016-2022
Universidad de Málaga
2003-2007
Ever since the first atomic structure of an enzyme was solved, discovery mechanism and dynamics reactions catalyzed by biomolecules has been key goal for understanding molecular processes that drive life on earth. Despite a large number successful methods trapping reaction intermediates, direct observation ongoing possible only in rare exceptional cases.
Mix-and-inject serial crystallography (MISC) is a technique designed to image enzyme catalyzed reactions in which small protein crystals are mixed with substrate just prior being probed by an X-ray pulse. This approach offers several advantages over flow cell studies. It provides (i) room temperature structures at near atomic resolution, (ii) time resolution ranging from microseconds seconds, and (iii) convenient reaction initiation. outruns radiation damage using femtosecond pulses allowing...
Here, we illustrate what happens inside the catalytic cleft of an enzyme when substrate or ligand binds on single-millisecond timescales. The initial phase enzymatic cycle is observed with near-atomic resolution using most advanced X-ray source currently available: European XFEL (EuXFEL). high repetition rate EuXFEL combined our mix-and-inject technology enables ceftriaxone binding to
To analyse the morphological and ultrastructural effects of lipopeptides cell-free liquid cultures from antagonistic Bacillus subtilis strains, UMAF6614 UMAF6639, on cucurbit powdery mildew fungus, Podosphaera fusca, conidial germination.Butanolic extracts supernatants B. were tested for their ability to arrest P. fusca germination using zucchini cotyledon disc method. Previously, occurrence lipopeptide antibiotics fengycin, iturin/bacillomycin surfactin in was verified by diverse...
Bypassing nature’s evolutionary trajectory, de novo protein generation—defined as creating artificial sequences from scratch—could enable breakthrough solutions for biomedical and environmental challenges. Viewing amino acid a language, we demonstrate that deep learning-based language model can generate functional across families, akin to generating grammatically semantically correct natural sentences on diverse topics. Our is trained by simply learning predict the next over 280 million...
Abstract We studied at the light and electron microscopic levels nitric oxide–producing neurons in mouse claustrum. Nicotinamide adenine dinucleotide phosphate (NADPH)‐diaphorase histochemistry neuronal oxide synthase (nNOS) immunohistochemical staining were used to reveal putative nitrergic neurons. also analyzed colocalization of nNOS with inhibitory neurotransmitter γ‐aminobutyric acid (GABA) as well ontogenesis nNOS‐immunoreactive neurons, providing evidence for different populations The...
Marine cyanobacteria are infected by phages whose genomes encode ferredoxin (Fd) electron carriers. These Fds thought to redirect the energy harvested from light phage-encoded oxidoreductases that enhance viral fitness, but it is unclear how biophysical properties and partner specificities of phage relate those photosynthetic organisms. Here, results a bioinformatics analysis using sequence similarity network revealed most closely related cyanobacterial transfer electrons photosystems...
Peroxisomes are eukaryotic organelles that sequester critical oxidative reactions and process the resulting reactive oxygen species into less toxic byproducts. Peroxisome function formation coordinated by peroxins (PEX proteins) guide peroxisome biogenesis division shuttle proteins lumen membrane of organelle. Despite importance in plant metabolism development, no peroxin structures have been reported. Here we report X-ray crystal structure PEX4-PEX22 complex from reference Arabidopsis...
Carbapenem-resistant Enterobacteriaceae continue to threaten human health worldwide with few effective treatment options. New Delhi metallo--lactamase (NDM) enzymes are a contributing element that drive resistance many -lactam- and carbapenem-based antimicrobials. Many NDM inhibitors known, yet none clinically viable. In this study, we present characterize new class of NDM-1 based on pyridine-2,6-dithiocarboxylic acid metal complex scaffold. These complexes display varied unique activity...
Abstract Marine cyanobacteria are infected by phage whose genomes encode ferredoxin (Fd) electron carriers. While these Fds thought to redirect the energy harvested from light phage-encoded oxidoreductases that enhance viral fitness, it is not clear how biophysical properties and partner specificities of relate those in photosynthetic organisms. Bioinformatic analysis using a sequence similarity network revealed most closely related cyanobacterial transfer electrons photosystems involved...
Ever since the first atomic structure of an enzyme was solved, discovery mechanism and dynamics reactions catalyzed by biomolecules has been key goal for understanding molecular processes that drive life on earth. Despite a large number successful methods trapping reaction intermediates, direct observation ongoing possible only in rare exceptional cases. Here, we demonstrate general method capturing catalysis ‘in-action’ ‘mix-and-inject serial crystallography’. Specifically, follow catalytic...
Abstract In this study, we follow the diffusion and buildup of occupancy substrate ceftriaxone in M. tuberculosis β-lactamase BlaC microcrystals by structural analysis enzyme complex at single millisecond time resolution. We also show binding reaction an inhibitor, sulbactam, on a slower scale. use ‘mix-and-inject’ technique to initiate these reactions diffusion, determine resulting structures serial crystallography using ultrafast, intense X-ray pulses from European XFEL (EuXFEL) arriving...
The visualization of protein motions is one the many exciting, cutting-edge uses an X-ray free electron laser.Time-resolved mix-and-inject-serial (MISC) crystallography studies have directly visualized reaction catalyzed by enzyme, β-lactamase (Olmos et al.).This class enzymes confers antibiotic resistance hydrolyzing a broad spectrum antibiotics in bacteria, including Mycobacterium tuberculosis.The previous MISC results using thirdgeneration antibiotic, ceftriaxone, showed development...