AI Article Synopsis
- Copper is essential for human health, but also toxic, necessitating careful regulation of its intake, distribution, and elimination.
- The study used advanced techniques like electron paramagnetic resonance spectroscopy and all-atom simulations to explore how copper travels within the body.
- Findings reveal that the copper-binding protein Atox1 interacts with a specific domain of ATP7B, suggesting that this binding occurs via weak, metal-stabilized interactions during the final stages of copper transport.
Article Abstract
Copper's essentiality and toxicity require a meticulous mechanism for its acquisition, cellular distribution and excretion, which remains hitherto elusive. Herein, we jointly employed electron paramagnetic resonance spectroscopy and all-atom simulations to resolve the copper trafficking mechanism in humans considering the route travelled by Cu(i) from the metallochaperone Atox1 to the metal binding domains 3 and 4 of ATP7B. Our study shows that Cu(i) in the final part of its extraction pathway is most likely mediated by binding of Atox1 monomer to MBD4 of ATP7B. This interaction takes place through weak metal-stabilized protein-protein interactions.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1039/c9mt00067d | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Conformational Dynamics of Mitochondrial Inorganic Pyrophosphatase hPPA2 and Its Changes Caused by Pathogenic Mutations.
Life (Basel)
January 2025
Chemistry Department, Lomonosov Moscow State University, 119991 Moscow, Russia.
Inorganic pyrophosphatases, or PPases, are ubiquitous enzymes whose activity is necessary for a large number of biosynthetic reactions. The catalytic function of PPases is dependent on certain conformational changes that have been previously characterized based on the comparison of the crystal structures of various complexes. The current work describes the conformational dynamics of a structural model of human mitochondrial pyrophosphatase hPPA2 using molecular dynamics simulation, all-atom principal component analysis, and coarse-grained normal mode analysis.
View Article and Find Full Text PDFDiscovery and Characterization of Two Selective Inhibitors for a Mu-Class Glutathione S-Transferase of 25 kDa from Using Computational and Bioinformatics Tools.
Biomolecules
December 2024
Departmento de Química, Universidad Autónoma Metropolitana-Iztapalapa, Mexico City C.P. 09310, Mexico.
Glutathione S-transferases (GSTs) are promising pharmacological targets for developing antiparasitic agents against helminths, as they play a key role in detoxifying cytotoxic xenobiotics and managing oxidative stress. Inhibiting GST activity can compromise parasite viability. This study reports the successful identification of two selective inhibitors for the mu-class glutathione S-transferase of 25 kDa (Ts25GST) from , named and , using a computationally guided approach.
View Article and Find Full Text PDFStructure-guided identification of mitogen-activated protein kinase-1 inhibitors towards anticancer therapeutics.
PLoS One
January 2025
Centre for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia, New Delhi, India.
Mitogen-activated protein kinase 1 (MAPK1) is a serine/threonine kinase that plays a crucial role in the MAP kinase signaling transduction pathway. This pathway plays a crucial role in various cellular processes, including cell proliferation, differentiation, adhesion, migration, and survival. Besides, many chemotherapeutic drugs targeting the MAPK pathway are used in clinical practice, and novel inhibitors of MAPK1 with improved specificity and efficacy are required.
View Article and Find Full Text PDFImplementation of Time-Averaged Restraints with UNRES Coarse-Grained Model of Polypeptide Chains.
J Chem Theory Comput
January 2025
Faculty of Chemistry, University of Gdańsk, Fahrenheit Union of Universities, ul. Wita Stwosza 63, 80-308 Gdańsk, Poland.
Time-averaged restraints from nuclear magnetic resonance (NMR) measurements have been implemented in the UNRES coarse-grained model of polypeptide chains in order to develop a tool for data-assisted modeling of the conformational ensembles of multistate proteins, intrinsically disordered proteins (IDPs) and proteins with intrinsically disordered regions (IDRs), many of which are essential in cell biology. A numerically stable variant of molecular dynamics with time-averaged restraints has been introduced, in which the total energy is conserved in sections of a trajectory in microcanonical runs, the bath temperature is maintained in canonical runs, and the time-average-restraint-force components are scaled up with the length of the memory window so that the restraints affect the simulated structures. The new approach restores the conformational ensembles used to generate ensemble-averaged distances, as demonstrated with synthetic restraints.
View Article and Find Full Text PDFFlexible Tail of Antimicrobial Peptide PGLa Facilitates Water Pore Formation in Membranes.
J Phys Chem B
January 2025
Research Center for Analytical Sciences, Tianjin Key Laboratory of Biosensing and Molecular Recognition, State Key Laboratory of Medicinal Chemical, Biology College of Chemistry, Nankai University, Tianjin 300071, China.
PGLa, an antimicrobial peptide (AMP), primarily exerts its antibacterial effects by disrupting bacterial cell membrane integrity. Previous theoretical studies mainly focused on the binding mechanism of PGLa with membranes, while the mechanism of water pore formation induced by PGLa peptides, especially the role of structural flexibility in the process, remains unclear. In this study, using all-atom simulations, we investigated the entire process of membrane deformation caused by the interaction of PGLa with an anionic cell membrane composed of dimyristoylphosphatidylcholine (DMPC) and dimyristoylphosphatidylglycerol (DMPG).
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!