The self-assembly of α-synuclein is closely associated with Parkinson’s disease and related syndromes. We show that squalamine, a natural product… Continue reading A natural product inhibits the initiation of α-synuclein aggregation and suppresses its toxicity
Leah Pandiscia, PhD
July 28, 2017
Leah Pandiscia, PhD
July 28, 2017
Cysteine-bound hemes are key components of many enzymes and biological sensors. Protonation (deprotonation) of the Cys ligand often accompanies redox… Continue reading Redox-dependent stability, protonation, and reactivity of cysteine-bound heme proteins
Leah Pandiscia, PhD
July 28, 2017
Leah Pandiscia, PhD
July 28, 2017
Fast protein folding involves complex dynamics in many degrees of freedom, yet microsecond folding experiments provide only low-resolution structural information.… Continue reading Mapping fast protein folding with multiple-site fluorescent probes
Leah Pandiscia, PhD
July 28, 2017
Aromatic polyketides make up a large class of natural products with diverse bioactivity. During biosynthesis, linear poly-β-ketone intermediates are regiospecifically… Continue reading Structural and functional analysis of two di-domain aromatase/cyclases from type II polyketide synthases
Leah Pandiscia, PhD
July 28, 2017
G-quadruplex (GQ) is a four stranded DNA secondary structure that arises from a guanine rich sequence. Stable formation of GQ… Continue reading Single-molecule imaging reveals a common mechanism shared by G-quadruplex–resolving helicases
Leah Pandiscia, PhD
July 28, 2017
Our understanding of how the endoplasmic reticulum (ER)-associated protein degradation (ERAD) machinery efficiently targets terminally misfolded proteins while avoiding the… Continue reading Htm1p–Pdi1p is a folding-sensitive mannosidase that marks N-glycoproteins for ER-associated protein degradation
Leah Pandiscia, PhD
July 28, 2017
Residue-level unfolding of two helix-turn-helix proteins—one naturally occurring and one de novo designed—is reconstructed from multiple sets of site-specific 13C isotopically… Continue reading Sequence, structure, and cooperativity in folding of elementary protein structural motifs
Leah Pandiscia, PhD
July 28, 2017
The ability to predictably control the coassembly of multiple nanoscale building blocks, especially those with disparate chemical and physical properties… Continue reading DNA-mediated engineering of multicomponent enzyme crystals
Leah Pandiscia, PhD
July 28, 2017
γ-Secretase is an intramembrane-cleaving protease that processes many type-I integral membrane proteins within the lipid bilayer, an event preceded by… Continue reading Nicastrin functions to sterically hinder γ-secretase–substrate interactions driven by substrate transmembrane domain
Leah Pandiscia, PhD
July 28, 2017
Bacterial biofilm formation during chronic infections confers increased fitness, antibiotic tolerance, and cytotoxicity. In many pathogens, the transition from a… Continue reading Mechanistic insights into c-di-GMP–dependent control of the biofilm regulator FleQ from Pseudomonas aeruginosa
Leah Pandiscia, PhD
July 28, 2017
Combinatorial biosynthesis aspires to exploit the promiscuity of microbial anabolic pathways to engineer the synthesis of new chemical entities. Fungal… Continue reading Diversity-oriented combinatorial biosynthesis of benzenediol lactone scaffolds by subunit shuffling of fungal polyketide synthases
Leah Pandiscia, PhD
July 28, 2017
Protein toxins from tarantula venom alter the activity of diverse ion channel proteins, including voltage, stretch, and ligandactivated cation channels.… Continue reading Structural interactions of a voltage sensor toxin with lipid membranes
Leah Pandiscia, PhD
July 28, 2017
Bacterial viruses of the P22-like family encode a specialized tail needle essential for genome stabilization after DNA packaging and implicated… Continue reading Structural Plasticity of the Protein Plug That Traps Newly Packaged Genomes in Podoviridae Virions
Leah Pandiscia, PhD
July 28, 2017
Leah Pandiscia, PhD
July 28, 2017
Antibodies with conformational specificity are important for detecting and interfering with polypeptide aggregation linked to several human disorders. We are… Continue reading Design and Optimization of Anti-amyloid Domain Antibodies Specific for β-Amyloid and Islet Amyloid Polypeptide
Leah Pandiscia, PhD
July 28, 2017
Escherichia coli harbors two highly conserved homologs of the essential mitochondrial respiratory complex II (succinate:ubiquinone oxidoreductase). Aerobically the bacterium synthesizes succinate:quinone… Continue reading Binding of the Covalent Flavin Assembly Factor to the Flavoprotein Subunit of Complex II
Leah Pandiscia, PhD
July 28, 2017
Leah Pandiscia, PhD
July 28, 2017
Bacterial cell membranes contain several protein pumps that resist the toxic effects of drugs by efficiently extruding them. One family… Continue reading Efflux by Small Multidrug Resistance Proteins Is Inhibited by Membrane-interactive Helix-stapled Peptides
Leah Pandiscia, PhD
July 28, 2017