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The heterodimerization of wild-type (WT) Cu, Zn superoxide dismutase-1 (SOD1) and mutant SOD1 might be a critical step in the pathogenesis of SOD1-linked amyotrophic lateral sclerosis (ALS). Post-translational modifications that accelerate SOD1 heterodimerization remain unidentified. Here, we used capillary electrophoresis to quantify the effect of cysteine-111 oxidation on the rate and free energy of ALS mutant/WT SOD1 heterodimerization. The oxidation of Cys111-β-SH to sulfinic and sulfonic acid (by hydrogen peroxide) increased rates of heterodimerization (with unoxidized protein) by ∼3-fold. Cysteine oxidation drove the equilibrium free energy of SOD1 heterodimerization by up to ΔΔG = −5.11 ± 0.36 kJ mol–1. Molecular dynamics simulations suggested that this enhanced heterodimerization, between oxidized homodimers and unoxidized homodimers, was promoted by electrostatic repulsion between the two “dueling” Cys111-SO2–/SO3–, which point toward one another in the homodimeric state. Together, these results suggest that oxidation of Cys-111 promotes subunit exchange between oxidized homodimers and unoxidized homodimers, regardless of whether they are mutant or WT dimers. 

Every living cell needs to get rid of leftover electrons when metabolism extracts energy through the oxidation of nutrients. Common soil microbes such as Geobacter sulfurreducens live in harsh environments that do not afford the luxury of soluble, ingestible electron acceptors like oxygen. Instead of resorting to fermentation, which requires the export of reduced compounds (e.g. ethanol or lactate derived from pyruvate) from the cell, these organisms have evolved a means to anaerobically respire by using nanowires to export electrons to extracellular acceptors in a process called extracellular electron transfer (EET) [ 1]. Since 2005, these nanowires were thought to be pili filaments [ 2]. But recent studies have revealed that nanowires are composed of multiheme cytochromes OmcS [ 3, 4] and OmcZ [ 5] whereas pili remain inside the cell during EET and are required for the secretion of nanowires [ 6]. However, how electrons are passed to these nanowires remains a mystery ( Figure 1A). Periplasmic cytochromes (Ppc) called PpcA-E could be doing the job, but only two of them (PpcA and PpcD) can couple electron/proton transfer — a necessary condition for energy generation. In a recent study, Salgueiro and co-workers selectively replaced an aromatic with an aliphatic residue to couple electron/proton transfer in PpcB and PpcE (Biochem. J. 2021, 478 (14): 2871–2887). This significant in vitro success of their protein engineering strategy may enable the optimization of bioenergetic machinery for bioenergy, biofuels, and bioelectronics applications. 

Octaethyltrioxopyrrocorphins unexpectedly show macrocycle-aromatic properties, even though they contain the macrocyclic π-system of the non-aromatic pyrrocorphins (hexahydroporphyrins). Two of the four possible triketone regioisomers were first reported in 1969 by one-pot oxidation of octaethylporphyrin but remained essentially unexplored since. We detail here the targeted preparation of the remaining two triketone isomers and the optical and NMR spectroscopic properties of all isomers. All four regioisomers possess unique electronic properties, including broadly varying degrees of diatropicity that were experimentally determined using 1 H NMR spectroscopy and computationally verified. Structural patterns modulating the aromaticity were recognized. These differences highlight the regioisomerically differentiated influences of the three β-oxo-functionalities. We also present the solid state structure of the two most common isomers (in their free base form or as zinc complexes), allowing further conclusions to be made about the resonance structures present in these triketones. Remarkably, also, the halochromic properties of the triketones differ sharply from those of regular (hydro)porphyrins, providing further support for the proposed 16-membered, 18 π-electron aromatic ring-current. The work conceptually expands the understanding of tris-modified hydroporphyrinoid analogues and the factors that enable and control porphyrinoid aromaticity. 

Blind and sighted persons can now share and visualize the same piece of data using tactile graphics that glow in ambient light. 

Light-induced microbial electron transfer has potential for efficient production of value-added chemicals, biofuels and biodegradable materials owing to diversified metabolic pathways. However, most microbes lack photoactive proteins and require synthetic photosensitizers that suffer from photocorrosion, photodegradation, cytotoxicity, and generation of photoexcited radicals that are harmful to cells, thus severely limiting the catalytic performance. Therefore, there is a pressing need for biocompatible photoconductive materials for efficient electronic interface between microbes and electrodes. Here we show that living biofilms ofGeobacter sulfurreducensuse nanowires of cytochrome OmcS as intrinsic photoconductors. Photoconductive atomic force microscopy shows up to 100-fold increase in photocurrent in purified individual nanowires. Photocurrents respond rapidly (<100 ms) to the excitation and persist reversibly for hours. Femtosecond transient absorption spectroscopy and quantum dynamics simulations reveal ultrafast (~200 fs) electron transfer between nanowire hemes upon photoexcitation, enhancing carrier density and mobility. Our work reveals a new class of natural photoconductors for whole-cell catalysis.