ATCUN-like Copper Site in βB2-Crystallin Plays a Protective Role in Cataract-Associated Aggregation.

Cataract is the leading cause of blindness worldwide, and it is caused by crystallin damage and aggregation. Senile cataractous lenses have relatively high levels of metals, while some metal ions can directly induce the aggregation of human γ-crystallins. Here, we evaluated the impact of divalent metal ions in the aggregation of human βB2-crystallin, one of the most abundant crystallins in the lens.

Copper Reductase Activity and Free Radical Chemistry by Cataract-Associated Human Lens γ-Crystallins.

Cataracts are caused by high-molecular-weight aggregates of human eye lens proteins that scatter light, causing lens opacity. Metal ions have emerged as important potential players in the etiology of cataract disease, as human lens γ-crystallins are susceptible to metal-induced aggregation. Here, the interaction of Cu ions with γD-, γC-, and γS-crystallins, the three most abundant γ-crystallins in the lens, has been evaluated.

Molecular Dynamics and Structural Studies of Zinc Chloroquine Complexes.

Chloroquine (CQ) is a first-choice drug against malaria and autoimmune diseases. It has been co-administered with zinc against SARS-CoV-2 and soon dismissed because of safety issues. The structural features of Zn-CQ complexes and the effect of CQ on zinc distribution in cells are poorly known.

Chloroquine disrupts zinc storage granules in primary Malpighian tubule cells of Drosophila melanogaster.

Contrasting reports exist in the literature regarding the effect of chloroquine treatment on cellular zinc uptake or secretion. Here, we tested the effect of chloroquine administration in the Drosophila model organism. We show that larvae grown on a diet supplemented with 2.

Tryptophan regulates zinc stores.

Zinc deficiency is commonly attributed to inadequate absorption of the metal. Instead, we show that body zinc stores in Drosophila melanogaster depend on tryptophan consumption. Hence, a dietary amino acid regulates zinc status of the whole insect—a finding consistent with the widespread requirement of zinc as a protein cofactor.

The Type 1 Blue Copper Site: From Electron Transfer to Biological Function.

Cupredoxins host in their scaffold one of the most studied and interesting metal sites in biology: the type 1 (T1) or blue Cu center. Blue Cu proteins have evolved to play key roles in biological electron transfer and have the ability to react with a wide variety of redox partners. The inner coordination sphere of T1 Cu sites conserves two histidines and one cysteine with a short Cu-S(Cys) bond as ligands in a trigonal arrangement, with a variable axial ligand that modulates the electronic structure and reactivity.

Anion Binding and Oxidative Modification at the Molybdenum Cofactor of Formate Dehydrogenase from Studied by X-ray Absorption Spectroscopy.

Formate dehydrogenase (FDH) enzymes are versatile catalysts for CO conversion. The FDH from contains a molybdenum cofactor with the dithiolene functions of two pyranopterin guanine dinucleotide molecules, a conserved cysteine, and a sulfido group bound at Mo(VI). In this study, we focused on metal oxidation state and coordination changes in response to exposure to O, inhibitory anions, and redox agents using X-ray absorption spectroscopy (XAS) at the Mo K-edge.

Light-driven hydrogen evolution catalyzed by a cobaloxime catalyst incorporated in a MIL-101(Cr) metal-organic framework.

A cobaloxime H evolution catalyst with a hydroxo-functionalized pyridine ligand, Co(dmgH)(4-HEP)Cl [dmgH = dimethylglyoxime, 4-HEP = 4-(2-hydroxyethyl)pyridine] was immobilized on a chromium terephthalate metal-organic framework (MOF), MIL-101(Cr), to construct a MOF-catalyst hybrid which displays good photocatalytic H evolution activity. The longevity of the cobaloxime catalyst is increased by MOF incorporation, but limited by the stability of the cobalt-pyridine bond under turnover conditions.

Kα X-ray Emission Spectroscopy on the Photosynthetic Oxygen-Evolving Complex Supports Manganese Oxidation and Water Binding in the S State.

The unique manganese-calcium catalyst in photosystem II (PSII) is the natural paragon for efficient light-driven water oxidation to yield O. The oxygen-evolving complex (OEC) in the dark-stable state (S) comprises a MnCaO core with five metal-bound water species. Binding and modification of the water molecules that are substrates of the water-oxidation reaction is mechanistically crucial but controversially debated.

Inhibitory and Non-Inhibitory NH Binding at the Water-Oxidizing Manganese Complex of Photosystem II Suggests Possible Sites and a Rearrangement Mode of Substrate Water Molecules.

The identity and rearrangements of substrate water molecules in photosystem II (PSII) water oxidation are of great mechanistic interest and addressed herein by comprehensive analysis of NH/NH binding. Time-resolved detection of O formation and recombination fluorescence as well as Fourier transform infrared (FTIR) difference spectroscopy on plant PSII membrane particles reveals the following. (1) Partial inhibition in NHCl buffer occurs with a pH-independent binding constant of ∼25 mM, which does not result from decelerated O formation, but from complete blockage of a major PSII fraction (∼60%) after reaching the Mn(IV) (S) state.

Effective intermediate-spin iron in O-transporting heme proteins.

Proteins carrying an iron-porphyrin (heme) cofactor are essential for biological O management. The nature of Fe-O bonding in hemoproteins is debated for decades. We used energy-sampling and rapid-scan X-ray Kβ emission and K-edge absorption spectroscopy as well as quantum chemistry to determine molecular and electronic structures of unligated (deoxy), CO-inhibited (carboxy), and O-bound (oxy) hemes in myoglobin (MB) and hemoglobin (HB) solutions and in porphyrin compounds at 20-260 K.

Spontaneous Si-C bond cleavage in (Triphos)-nickel complexes.

Herein, we report on the versatile reactions of CHC(CHPPh) as well as CHSi(CHPPh) derived Ni-complexes. While Ni[CHC(CHPPh)] complexes reveal high stability, the Ni[CHSi(CHPPh)] analogs show rapid decomposition at room temperature and afford the unprecedented pseudo-tetrahedral phosphino methanide complex 5. We provide a detailed electronic structure of 5 from X-ray absorption and emission spectroscopy data analysis in combination with DFT calculations, as well as from comparison with structurally related complexes.

Protonation State of MnFe and FeFe Cofactors in a Ligand-Binding Oxidase Revealed by X-ray Absorption, Emission, and Vibrational Spectroscopy and QM/MM Calculations.

Enzymes with a dimetal-carboxylate cofactor catalyze reactions among the top challenges in chemistry such as methane and dioxygen (O) activation. Recently described proteins bind a manganese-iron cofactor (MnFe) instead of the classical diiron cofactor (FeFe). Determination of atomic-level differences of homo- versus hetero-bimetallic cofactors is crucial to understand their diverse redox reactions.