Thiol, His-His Motif, and the Battle over Cu(II) in the Relationship of CopM Metallophore and OprC Outer Membrane Protein.

The mechanisms of Cu import across the bacterial outer membrane have been investigated only in a few cases. One such mechanism involves the outer membrane OprC transporter with a unique CxxxM-HxM metal-binding site, discovered recently. This newly identified site in OprC is located outside the cell and is, therefore, most likely to bind Cu(II) through this domain.

Cu(ii) binding to an antimicrobial shrimp peptide - a small step for structural chemistry, a big leap for medicinal applications.

PvHCt, a 23-amino acid long, histidine-rich peptide derived from shrimp, becomes strongly antimicrobial upon Cu(ii) ion binding. We describe Zn(ii) and Cu(ii) complexes of this peptide, aiming to understand how metal binding and structure correlates to biological activity. Using NMR, UV-vis, CD and FTIR spectroscopies, along with cyclic voltammetry, potentiometry, and DFT calculations, we demonstrate that Cu(ii) binds to the central and C-terminal regions of the peptide, inducing significant structural changes.

Mitigating diabetes associated with reactive oxygen species (ROS) and protein aggregation through pharmacological interventions.

Diabetes mellitus, a complex metabolic disorder, presents a growing global health challenge. In 2021, there were 529 million diabetics worldwide. At the super-regional level, Oceania, the Middle East, and North Africa had the highest age-standardized rates.

Impact of metal coordination and pH on the antimicrobial activity of histatin 5 and the products of its hydrolysis.

This work focuses on the relationship between the coordination chemistry and antimicrobial activity of Zn(II) and Cu(II) complexes of histatin 5 and the products of its hydrolysis: its N-terminal fragment (histatin 5-8) and C-terminal fragment (histatin 8). Cu(II) coordinates in an albumin-like binding mode and Zn(II) binds to up to 3 His imidazoles. The antimicrobial activity of histatins and their metal complexes (i) strongly depends on pH - they are more active at pH 5.

Beyond copper: examining the significance of His-mutations in mycobacterial GroEL1 HRCT for Ni(II) complex stability and formation.

Recently, we have studied the coordination chemistry of the Cu(II)-histidine-rich C-terminal tail (HRCT) complex of the mycobacterial GroEL1 protein. The structure of this domain differs significantly compared to the well-known methionine-glycine-rich GroEL chaperonin - it was predicted that mycobacterial GroEL1 could play a significant role in the metal homeostasis of , especially copper. However, we found that this particular domain's pattern also repeats in a number of Ni(II)-binding proteins.

Copper Forms a PPII Helix-Like Structure with the Catalytic Domains of Bacterial Zinc Metalloproteases.

The rapid spread of antibiotic-resistant bacteria continuously raises concerns about the future ineffectiveness of current antimicrobial treatments against infectious diseases. To address this problem, new therapeutic strategies and antimicrobial drugs with unique modes of action are urgently needed. Inhibition of metalloproteases, bacterial virulence factors, is a promising target for the development of antibacterial treatments.

A Combined NMR and UV-Vis Approach to Evaluate Radical Scavenging Activity of Rosmarinic Acid and Other Polyphenols.

Oxidative stress results from an imbalance between reactive oxygen species (ROS) production and the body's ability to neutralize them. ROS are reactive molecules generated during cellular metabolism and play a crucial role in normal physiological processes. However, excessive ROS production can lead to oxidative damage, contributing to various diseases and aging.

Semenogelins Armed in Zn(II) and Cu(II): May Bioinorganic Chemistry Help Nature to Cope with ?

Proteolytic degradation of semenogelins, the most abundant proteins from human semen, results in the formation of 26- and 29-amino acid peptides (SgIIA and SgI-29, respectively), which share a common 15 amino acid fragment (Sg-15). All three ligands are effective Zn(II) and Cu(II) binders; in solution, a variety of differently metalated species exist in equilibrium, with the [NH, 3N] donor set prevailing at physiological pH in the case of both metals. For the first time, the Cu(II)-induced antimicrobial activity of Sg-15 against is shown.

Bioinorganic Chemistry of Micronutrients Related to Alzheimer's and Parkinson's Diseases.

Metal ions are fundamental to guarantee the regular physiological activity of the human organism. Similarly, vitamins play a key role in many biological functions of the metabolism, among which are coenzymes, redox mediators, and antioxidants. Due to their importance in the human organism, both metals and vitamins have been extensively studied for their involvement in neurodegenerative diseases (NDs).

Copper Binding and Redox Activity of α-Synuclein in Membrane-Like Environment.

α-Synuclein (αSyn) constitutes the main protein component of Lewy bodies, which are the pathologic hallmark in Parkinson's disease. αSyn is unstructured in solution but the interaction of αSyn with lipid membrane modulates its conformation by inducing an α-helical structure of the -terminal region. In addition, the interaction with metal ions can trigger αSyn conformation upon binding and/or through the metal-promoted generation of reactive oxygen species which lead to a cascade of structural alterations.

A Comparative Study between Lycorine and Galantamine Abilities to Interact with AMYLOID β and Reduce In Vitro Neurotoxicity.

Galantamine is a natural alkaloid extracted from the plants and is used as the active ingredient of a drug approved for the treatment of the early stages of Alzheimer's disease. It mainly acts as an acetylcholinesterase (AChE) inhibitor, increasing concentrations of the acetylcholine neurotransmitter. Recent cellular studies have also shown the ability of galantamine to protect SH-SY5Y cell lines against amyloid-β (Aβ)-induced toxicity.

Metal specificity of the Ni(II) and Zn(II) binding sites of the N-terminal and G-domain of HypB.

HypB is one of the chaperones required for proper nickel insertion into [NiFe]-hydrogenase. HypB has two potential Ni(II) and Zn(II) binding sites-the N-terminal one and the so-called GTPase one. The metal-loaded HypB-SlyD metallochaperone complex activates nickel release from the N-terminal HypB site.

Metal Complexation Mechanisms of Polyphenols Associated to Alzheimer's Disease.

Polyphenols are a class of compounds, produced by plants, which share the ability to act as potent antioxidants. First investigations on polyphenols' antioxidant activity are dated almost twenty years ago when their relationship and implication with the prevention and treatment of cancer was proposed for the first time. Later, in the early 2000s, the neuroprotective effects of several polyphenols were demonstrated.

Dynamic Interplay between Copper Toxicity and Mitochondrial Dysfunction in Alzheimer's Disease.

Alzheimer's disease (AD) is a neurodegenerative disorder, affecting millions of people worldwide, a number expected to exponentially increase in the future since no effective treatments are available so far. AD is characterized by severe cognitive dysfunctions associated with neuronal loss and connection disruption, mainly occurring in specific brain areas such as the hippocampus, cerebral cortex, and amygdala, compromising memory, language, reasoning, and social behavior. Proteomics and redox proteomics are powerful techniques used to identify altered proteins and pathways in AD, providing relevant insights on cellular pathways altered in the disease and defining novel targets exploitable for drug development.

Novel Perspective on Alzheimer's Disease Treatment: Rosmarinic Acid Molecular Interplay with Copper(II) and Amyloid β.

Alzheimer's disease is a severe disorder that affects millions of people worldwide. It is a very debilitating disease with no cure at the moment. The necessity of finding an effective treatment is very demanding, and the entire scientific community is putting in a lot of effort to address this issue.

Metal Complexes of Two Specific Regions of ZnuA, a Periplasmic Zinc(II) Transporter from .

The crystal structure of ZnZnuA from reveals two metal binding sites. (i) The primary binding site, His143, is located close the His-rich loop (residues 116-138) and plays a significant role in Zn(II) acquisition. (ii) The secondary binding site involves His224.