A5088088910- Earthquake Detection and Analysis
- Seismic Waves and Analysis
- Ionosphere and magnetosphere dynamics
- Astrophysics and Cosmic Phenomena
- Methane Hydrates and Related Phenomena
- Seismology and Earthquake Studies
- Metabolism and Genetic Disorders
- Superconducting Materials and Applications
- Enzyme Structure and Function
- Particle accelerators and beam dynamics
- Magnetic confinement fusion research
- Metabolomics and Mass Spectrometry Studies
- Biochemical effects in animals
- Biochemical and Molecular Research
- GABA and Rice Research
- Microbial Metabolic Engineering and Bioproduction
- Hepatitis B Virus Studies
- Muscle metabolism and nutrition
- RNA and protein synthesis mechanisms
- Protein Structure and Dynamics
- Viral Infections and Vectors
- Viral Infections and Outbreaks Research
- Folate and B Vitamins Research
- Amino Acid Enzymes and Metabolism
- Biotin and Related Studies
La Jolla Institute for Immunology
2020-2023
California Institute of Technology
2022
Drexel University
2016-2020
Fox Chase Cancer Center
2016-2020
Temple University Health System
2016-2019
Scripps (United States)
2019
Scripps Institution of Oceanography
2019
University of Missouri
2008
Monoclonal antibodies can provide important pre- or post-exposure protection against infectious disease for those not yet vaccinated in individuals that fail to mount a protective immune response after vaccination. Inmazeb (REGN-EB3), three-antibody cocktail Ebola virus, lessened and improved survival controlled trial. Here, we present the cryo-EM structure at 3.1 Å of virus glycoprotein, determined without symmetry averaging, simultaneous complex with cocktail. This allows modeling...
Improved understanding of the relationship among structure, dynamics, and function for enzyme phenylalanine hydroxylase (PAH) can lead to needed new therapies phenylketonuria, most common inborn error amino acid metabolism. PAH is a multidomain homo-multimeric protein whose conformation multimerization properties respond allosteric activation by substrate (Phe); regulation necessary maintain Phe below neurotoxic levels. A recently introduced model involves major domain motions...
Phenylalanine hydroxylase (PAH) regulates phenylalanine (Phe) levels in mammals to prevent neurotoxicity resulting from high Phe concentrations as observed genetic disorders leading hyperphenylalaninemia and phenylketonuria. PAH senses elevated by transient allosteric binding a protein-protein interface between ACT domains of different subunits tetramer. This is present an activated (A-PAH) tetramer absent resting-state (RS-PAH) To investigate this sensing mechanism, here we used the GROMACS...
Phenylalanine hydroxylase (PAH) is an allosteric enzyme that maintains phenylalanine (Phe) below neurotoxic levels; its failure results in phenylketonuria, inborn error of amino acid metabolism. Wild type (WT) PAH equilibrates among resting-state (RS-PAH) and activated (A-PAH) conformations, whose equilibrium position depends upon Phe binding. The RS-PAH conformation WT rat (rPAH) contains a cation-π sandwich involving Phe80 cannot exist the A-PAH conformation. variants F80A, F80D, F80L,...
Phenylalanine hydroxylase (PAH) is an allosteric enzyme responsible for maintaining phenylalanine (Phe) below neurotoxic levels; its failure results in phenylketonuria (PKU). PAH equilibrates among long‐lived conformations, including resting‐state (RS‐PAH) and activated (A‐PAH), whose equilibrium position depends upon Phe binding to the A‐PAH conformation. The RS‐PAH conformation contains a stabilizing cation‐pi sandwich between Phe80, Arg123, Arg240 (PDB entry 5DEN), which cannot exist...
Abstract Monoclonal antibodies can provide important pre- or post-exposure protection against disease for those not yet vaccinated in individuals that fail to mount a protective immune response after vaccination. A key concern use of monotherapy monoclonal antibody products lies the high risk mutagenic escape. Inmazeb (REGN-EB3), three-antibody cocktail Ebola virus, demonstrated efficacy lessening course and improving survival randomized, controlled trial. Here we present cryoEM structure at...
Increasing numbers of proteins are being revealed to “shape shift” in physiologically relevant ways that do not dramatically alter secondary structure. As each has been discovered they have called morpheeins, transformers, metamorphic polymorphs, and others. In case the alternate assemblies different functions ranging from “on vs. off” “moonlighting”. These examples continue surprise their discoverers because defy “one sequence, one structure, function” paradigm an unexpected way. likely as...
ABSTRACT Phenylalanine hydroxylase (PAH) is an allosteric enzyme responsible for maintaining phenylalanine (Phe) below neurotoxic levels; its failure results in phenylketonuria. Wild type (WT) PAH equilibrates among resting-state (RS-PAH) and activated (A-PAH) conformations, whose equilibrium position depends upon Phe binding to the A-PAH conformation. The RS-PAH conformation of WT rat (rPAH) contains a cation-π sandwich between Phe80, Arg123, Arg420, which cannot exist Phe80 variants F80A,...