Bernard Have (scalezephyr3)

The catalytic reduction of CO2 to HCO2- requires a formal transfer of a hydride (two electrons, one proton). Synthetic approaches for inorganic molecular catalysts have exclusively relied on classic metal hydrides, where the proton and electrons originate from the metal (via heterolytic cleavage of an M-H bond). An analysis of the scaling relationships that exist in classic metal hydrides reveal that hydride donors sufficiently hydridic to perform CO2 reduction are only accessible at very reducing electrochemical potentials, which is consistent with known synthetic electrocatalysts. By comparison, the formate dehydrogenase enzymes operate at relatively mild potentials. SL327 In contrast to reported synthetic catalysts, none of the major mechanistic proposals for hydride transfer in formate dehydrogenase proceed through a classic metal hydride. Instead, they invoke formal hydride transfer from an orthogonal or bidirectional mechanism, where the proton and electrons are not colocated. We discuss the thermodynamic advantages of this approach for favoring CO2 reduction at mild potentials, along with guidelines for replicating this strategy in synthetic systems.We demonstrate photoresponsive cholesteric liquid crystals (CLCs) doped with glycomacrocyclic azobenzene derivatives, which exhibit large conformational changes, providing dynamic control of helical superstructures in response to a light stimulus. An unprecedented shortening of the helical pitch length and the empowerment of helical twisting power up to 500% are observed upon trans (E) to cis (Z) photoisomerization. Light-driven dynamic helix twisting and untwisting behavior affords the first example of glycomacrocyclic azobenzene-based CLCs, which can drive the mechanical movement of micro-objects. Two modes of rotation-two-directional or one-directional rotational motion (crankshaft mode)-are realized. In particular, the latter mode based on the reversible cholesteric texture transition between homogeneous stripes and focal conics leads to the accumulation of the rotation angles achieving the amplified mechanical movements.Niemann Pick type C2 (NPC2) is a small sterol binding protein in the lumen of late endosomes and lysosomes. We showed recently that the yeast homologue of NPC2 together with its binding partner NCR1 mediates integration of ergosterol, the main sterol in yeast, into the vacuolar membrane. Here, we study the binding specificity and the molecular details of lipid binding to yeast NPC2. We find that NPC2 binds fluorescence- and spin-labeled analogues of phosphatidylcholine (PC), phosphatidylserine, phosphatidylinositol (PI), and sphingomyelin. Spectroscopic experiments show that NPC2 binds lipid monomers in solution but can also interact with lipid analogues in membranes. We further identify ergosterol, PC, and PI as endogenous NPC2 ligands. Using molecular dynamics simulations, we show that NPC2's binding pocket can adapt to the ligand shape and closes around bound ergosterol. Hydrophobic interactions stabilize the binding of ergosterol, but binding of phospholipids is additionally stabilized by electrostatic interactions at the mouth of the binding site. Our work identifies key residues that are important in stabilizing the binding of a phospholipid to yeast NPC2, thereby rationalizing future mutagenesis studies. Our results suggest that yeast NPC2 functions as a general "lipid solubilizer" and binds a variety of amphiphilic lipid ligands, possibly to prevent lipid micelle formation inside the vacuole.With the spread of drug resistance, new antimicrobials are urgently needed. Here, we set out to tackle this problem by high-throughput exploration for novel antifungal synergies among combinations of approved, nonantifungal drugs; a novel strategy exploiting the potential of alternative targets, low chemicals usage and low development risk. We screened the fungal pathogen Candida albicans by combining a small panel of nonantifungal drugs (all in current u