Fe(II), Mn(II), and Zn(II) Binding to the C-Terminal Region of FeoB Protein: An Insight into the Coordination Chemistry and Specificity of the Escherichia coli Fe(II) Transporter.

The interactions between two peptide ligands [Ac763CCAASTTGDCH773 (P1) and Ac743RRARSRVDIELLATRKSVSSCCAASTTGDCH773 (P2)] derived from the cytoplasmic C-terminal region of Eschericha coli FeoB protein and Fe(II), Mn(II), and Zn(II) ions were investigated. The Feo system is regarded as the most important bacterial Fe(II) acquisition system, being one of the key virulence factors, especially in anaerobic conditions. Located in the inner membrane of Gram-negative bacteria, FeoB protein transports Fe(II) from the periplasm to the cytoplasm. Despite its crucial role in bacterial pathogenicity, the mechanism in which the metal ion is trafficked through the membrane is not yet elucidated. In the gammaproteobacteria class, the cytoplasmic C-terminal part of FeoB contains conserved cysteine, histidine, and glutamic and aspartic acid residues, which could play a vital role in Fe(II) binding in the cytoplasm, receiving the metal ion from the transmembrane helices. In this work, we characterized the complexes formed between the whole cytosolic C-terminal sequence of E. coli FeoB (P2) and its key polycysteine region (P1) with Fe(II), Mn(II), and Zn(II) ions, exploring the specificity of the C-terminal region of FeoB. With the help of a variety of potentiometric, spectroscopic (electron paramagnetic resonance and NMR), and spectrometric (electrospray ionization mass spectrometry) techniques and molecular dynamics, we propose the metal-binding modes of the ligands, compare their affinities toward the metal ions, and discuss the possible physiological role of the C-terminal region of E. coli FeoB.

Zn2+ and Cu2+ Interaction with the Recognition Interface of ACE2 for SARS-CoV-2 Spike Protein.

The spike protein (S) of SARS-CoV-2 is able to bind to the human angiotensin-converting enzyme 2 (ACE2) receptor with a much higher affinity compared to other coronaviruses. The binding interface between the ACE2 receptor and the spike protein plays a critical role in the entry mechanism of the SARS-CoV-2 virus. There are specific amino acids involved in the interaction between the S protein and the ACE2 receptor. This specificity is critical for the virus to establish a systemic infection and cause COVID-19 disease. In the ACE2 receptor, the largest number of amino acids playing a crucial role in the mechanism of interaction and recognition with the S protein is located in the C-terminal part, which represents the main binding region between ACE2 and S. This fragment is abundant in coordination residues such as aspartates, glutamates, and histidine that could be targeted by metal ions. Zn2+ ions bind to the ACE2 receptor in its catalytic site and modulate its activity, but it could also contribute to the structural stability of the entire protein. The ability of the human ACE2 receptor to coordinate metal ions, such as Zn2+, in the same region where it binds to the S protein could have a crucial impact on the mechanism of recognition and interaction of ACE2-S, with consequences on their binding affinity that deserve to be investigated. To test this possibility, this study aims to characterize the coordination ability of Zn2+, and also Cu2+ for comparison, with selected peptide models of the ACE2 binding interface using spectroscopic and potentiometric techniques.

Regional Comparisons of Associations Between Physical Activity Levels and Cardiovascular Disease: The Story of Atlantic Canada.

BACKGROUND: Physical inactivity is an important risk factor for cardiovascular disease (CVD). Atlantic Canada is a region with lower physical activity (PA) levels and poorer CVD outcomes than the rest of Canada. Yet, within-region variation is expected. This study aimed to assess the association between PA and CVD and how this relationship varied on a regional level. METHODS: This cross-sectional study used data from the Atlantic Partnership for Tomorrow's Health (PATH) Study. The cohort included 823 CVD cases and 2469 age-, sex-, and province of residence-matched controls between the ages 35 and 69. Data collected included self-reported CVD and PA levels as well as information on sociodemographic characteristics, health status, and lifestyle behaviours. Simple and multiple logistic regression were used to assess the association between PA and CVD. RESULTS: High PA levels were associated with a 26% reduction in the mean probability of CVD compared with low PA levels across the total population. Compared with high PA levels, moderate and low PA levels were associated with increased odds of CVD across all 4 provinces. However, regional variation was observed, with higher odds of CVD for low-to-moderate PA levels in Newfoundland and Labrador and New Brunswick compared with Nova Scotia and Prince Edward Island. CONCLUSIONS: Atlantic Canadians experience regional inequalities in the association between PA and CVD. Future work needs to explore underlying pathways driving these regional differences, which may be the impetus for interventions that mitigate risk and CVD burden in populations of greatest need.

INTRODUCTION: L'inactivité physique est un facteur de risque important de maladies cardiovasculaires (MCV). Le Canada atlantique est une région où les taux d'activité physique (AP) sont faibles et les issues des MCV sont moins bonnes que dans le reste du pays. Cependant, on s'attend à des variations entre les régions. La présente étude a pour objectif d'évaluer l'association entre l'AP et les MCV, et la façon dont cette relation varie sur le plan régional. MÉTHODES: Cette étude transversale a utilisé les données de l'étude La VOIE atlantique (le Partenariat de l'Atlantique pour la santé de demain). La cohorte comptait 823 cas de MCV et 2 469 témoins de 35 à 69 ans appariés selon l'âge, le sexe et la province de résidence. Les données collectées étaient les suivantes : les MCV et les taux d'AP, ainsi que les renseignements sur les caractéristiques sociodémographiques, l'état de santé et les comportements liés au mode de vie. Nous avons utilisé la régression logistique simple et multiple pour évaluer l'association entre l'AP et les MCV. RÉSULTATS: Les taux élevés d'AP ont été associés à une réduction de 26 % de la probabilité moyenne des MCV comparativement à des taux faibles d'AP dans l'ensemble de la population. Comparativement à des taux élevés d'AP, les taux faibles et modérés d'AP ont été associés à une probabilité accrue de MCV dans les 4 provinces. Toutefois, nous avons observé des variations régionales lors de taux faibles à modérés d'AP, soit une probabilité plus élevée de MCV à Terre-Neuve-et-Labrador et au Nouveau-Brunswick qu'en Nouvelle-Écosse et à l'Île-du-Prince-Édouard. CONCLUSIONS: Les Canadiens de l'Atlantique montrent des inégalités régionales dans l'association entre l'AP et les MCV. D'autres travaux sont nécessaires pour étudier les voies sous-jacentes entraînant ces différences régionales et peuvent donner lieu à des interventions qui allègent le risque et le fardeau des MCV au sein des populations dont les besoins sont les plus grands.