A5014985272- Protein Structure and Dynamics
- Pesticide and Herbicide Environmental Studies
- Environmental Toxicology and Ecotoxicology
- Pharmaceutical and Antibiotic Environmental Impacts
- Pesticide Exposure and Toxicity
- Biochemical Acid Research Studies
- RNA and protein synthesis mechanisms
- RNA Research and Splicing
- Diffusion and Search Dynamics
- Enzyme Catalysis and Immobilization
- Insect and Pesticide Research
- Microtubule and mitosis dynamics
- Mass Spectrometry Techniques and Applications
- Photosynthetic Processes and Mechanisms
- Force Microscopy Techniques and Applications
- Phytochemicals and Antioxidant Activities
- Medicinal plant effects and applications
- Click Chemistry and Applications
- Organic Chemistry Cycloaddition Reactions
- Fungal Biology and Applications
Weizmann Institute of Science
2019-2023
Intrinsically disordered proteins often form dynamic complexes with their ligands. Yet, the speed and amplitude of these motions are hidden in classical binding kinetics. Here, we directly measure dynamics an exceptionally mobile, high-affinity complex. We show that tail cell adhesion protein E-cadherin dynamically samples a large surface area protooncogene β-catenin. Single-molecule experiments molecular simulations resolve high resolution space time. Contacts break within hundreds...
Abstract Evolutionary trajectories are deemed largely irreversible. In a newly diverged protein, reversion of mutations that led to the functional switch typically results in loss both new and ancestral functions. Nonetheless, evolutionary transitions where reversions viable have also been described. The structural mechanistic causes compatibility versus incompatibility therefore remain unclear. We examined two laboratory evolution mammalian paraoxonase-1, lactonase with promiscuous...
Anthropogenic organophosphorus compounds (AOPCs), such as phosphotriesters, are used extensively plasticizers, flame retardants, nerve agents, and pesticides. To date, only a handful of soil bacteria bearing phosphotriesterase (PTE), the key enzyme in AOPC degradation pathway, have been identified. Therefore, extent to which capable utilizing AOPCs phosphorus source, how widespread this adaptation may be, remains unclear. Marine environments with limitation increasing levels pollution by...
Nerve agents are organophosphates (OPs) that potently inhibit acetylcholinesterase, and their enzymatic detoxification has been a long-standing goal. vary widely in size, charge, hydrophobicity the cleavable ester bond. A single enzyme is therefore unlikely to efficiently hydrolyze all agents. Here, we describe mixture of three previously developed variants bacterial phosphotriesterase (Bd-PTE) highly stable nearly sequence identical. This enables effective broad spectrum known threat...
Abstract Quinone methide (QM) chemistry is widely applied including in enzyme inhibitors. Typically, enzyme‐mediated bond breaking releases a phenol product that rearranges into an electrophilic QM turn covalently modifies protein side chains. However, the factors govern reactivity of QM‐based inhibitors and their mode inhibition have not been systematically explored. Foremost, inactivation might occur cis , whereby molecule inactivates very same released it, or by trans if QMs diffuse away...
Abstract Specific protein interactions typically require well-shaped binding interfaces. Here, we report a cunning exception. The disordered tail of the cell-adhesion E-cadherin dynamically samples large surface area proto-oncogene β-catenin. Single-molecule experiments and molecular simulations resolve these motions with high resolution in space time. Contacts break form within hundreds microseconds without dissociation complex. A few persistent provide specificity whereas unspecific...
Abstract Nerve agents are organophosphates that potently inhibit acetylcholinesterase and their enzymatic detoxification has been a long-standing goal. vary widely in size, charge, hydrophobicity, the cleavable ester bond. A single enzyme is therefore unlikely to efficiently hydrolyze all agents. Here, we describe mixture of three previously developed variants bacterial phosphotriesterase ( Bd -PTE) highly stable nearly sequence identical. This enables effective broad spectrum known threat –...
Abstract Anthropogenic organophosphates (AOPs), such as phosphotriesters, are used extensively plasticizers, flame retardants, nerve agents and pesticides. Soil bacteria bearing a phosphotriesterase (PTE) can degrade AOPs, but whether capable of utilizing AOPs phosphorus source, how widespread PTEs in nature, remains unclear. Here, we report the utilization diverse by four model marine seventeen bacterial isolates from seawater samples. To unravel details AOP utilization, two novel were...