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Dubovetskyi, A.

Publications and source records attributed to Dubovetskyi, A..

3 recordsLinked to original sources

Widespread Utilization of Diverse Organophosphate Pollutants by Marine Bacteria

Anthropogenic organophosphates (AOPs), such as phosphotriesters, are used extensively as plasticizers, flame retardants, nerve agents and pesticides. Soil bacteria bearing a phosphotriesterase (PTE) can degrade AOPs, but whether bacteria are capable of utilizing AOPs as a phosphorus source, and how widespread PTEs are in nature, remains unclear. Here, we report the utilization of diverse AOPs by four model marine bacteria and seventeen bacterial isolates from seawater samples. To unravel the details of AOP utilization, two novel PTEs from marine bacteria were isolated and characterized. When expressed in E. coli, these PTEs enabled growth on a pesticide analog as the sole phosphorus source. Utilization of AOPs provides bacteria with a source of phosphorus in depleted environments and offers a new prospect for the bioremediation of a pervasive class of anthropogenic pollutants. One sentence summaryWidespread utilization of diverse organophosphate pollutants by over 20 marine bacterial strains represents a new hope for ocean bioremediation.

microbiology↗

Diffusion of the disordered E-cadherin tail on β-catenin

Specific protein interactions typically require well-shaped binding interfaces. Here, we report a cunning exception. The disordered tail of the cell-adhesion protein E-cadherin dynamically samples a large surface area of the proto-oncogene {beta}-catenin. Single-molecule experiments and molecular simulations resolve these motions with high resolution in space and time. Contacts break and form within hundreds of microseconds without dissociation of the complex. A few persistent interactions provide specificity whereas unspecific contacts boost affinity. The energy landscape of this complex is rugged with many small barriers (3 - 4 kBT) and reconciles specificity, high affinity, and extreme disorder. Given the roles of {beta}-catenin in cell-adhesion, signalling, and cancer, this Velcro-like design has the potential to tune the stability of the complex without requiring dissociation.

biophysics↗

A mixture of three engineered phosphotriesterases enables rapid detoxification of the entire spectrum of known threat nerve agents

Nerve agents are organophosphates that potently inhibit acetylcholinesterase and their enzymatic detoxification has been a long-standing goal. Nerve agents vary widely in size, charge, hydrophobicity, and the cleavable ester bond. A single enzyme is therefore unlikely to efficiently hydrolyze all agents. Here, we describe a mixture of three previously developed variants of the bacterial phosphotriesterase (Bd-PTE) that are highly stable and nearly sequence identical. This mixture enables effective detoxification of a broad spectrum of known threat agents - GA (tabun), GB (sarin), GD (soman), GF (cyclosarin), VX, and Russian-VX. The potential for dimer dissociation and exchange that could inactivate Bd-PTE has minimal impact, and the three enzyme variants are as active in a mixture as they are individually. To our knowledge, this engineered enzyme cocktail comprises the first solution for enzymatic detoxification of the entire range of threat nerve agents.

biochemistry↗