Selective oxidation of active site aromatic residues in engineered Cu proteins.

Recent studies have revealed critical roles for the local environments surrounding metallocofactors, such as the newly identified Cu site in particulate methane monooxygenases (pMMOs) and the second sphere aromatic residues in lytic polysaccharide monooxygenases (LPMOs), implicated in the protection against oxidative damage. However, these features are subjects of continued debate. Our work utilizes biotin-streptavidin (Sav) technology to develop artificial metalloproteins (ArMs) that mimic the active sites of natural copper metalloenzymes.

A versatile bioluminescent probe with tunable color.

Bioluminescence is a powerful method for imaging , but applications at the microscale are far from routine. This is due, in part, to a lack of versatile tools for visualizing dynamic events. To address this void, we developed a new platform-Bioluminescence Resonance Energy mAKe over with a Fluorescence-Activating absorption-Shifting Tag (BREAKFAST).

Accessing a synthetic FeMn core to model biological heterobimetallic active sites.

Metalloproteins with dinuclear cores are known to bind and activate dioxygen, with a subclass of these proteins having active sites containing FeMn cofactors and activities ranging from long-range proton-coupled electron transfer (PCET) to post-translational peptide modification. While mechanistic studies propose that these metallocofactors access FeMn intermediates, there is a dearth of related synthetic analogs. Herein, the first well-characterized synthetic Fe-(μ-O)-Mn complex is reported; this complex shows similar spectroscopic features as the catalytically competent FeMn intermediate X found in Class Ic ribonucleotide reductase and demonstrates PCET function towards phenolic substrates.

Point mutations in SARS-CoV-2 variants induce long-range dynamical perturbations in neutralizing antibodies.

Monoclonal antibodies are emerging as a viable treatment for the coronavirus disease 19 (COVID-19). However, newly evolved variants of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can reduce the efficacy of currently available antibodies and can diminish vaccine-induced immunity. Here, we demonstrate that the microscopic dynamics of neutralizing monoclonal antibodies can be profoundly modified by the mutations present in the spike proteins of the SARS-COV-2 variants currently circulating in the world population.

Markov state models and NMR uncover an overlooked allosteric loop in p53.

The tumor suppressor p53 is the most frequently mutated gene in human cancer, and thus reactivation of mutated p53 is a promising avenue for cancer therapy. Analysis of wildtype p53 and the Y220C cancer mutant long-timescale molecular dynamics simulations with Markov state models and validation by NMR relaxation studies has uncovered the involvement of loop L6 in the slowest motions of the protein. Due to its distant location from the DNA-binding surface, the conformational dynamics of this loop has so far remained largely unexplored.

From bench to bedside: the growing use of translational research in cancer medicine.

Cancer is responsible for one in eight deaths worldwide, with more than twelve million new cases diagnosed yearly. A large percentage of patients die after developing cancer despite aggressive treatment, indicating a need for new approaches to cancer therapy. The push for development of novel diagnostic and therapeutic agents has allowed translational cancer research to flourish.