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Charge Reversal of the Uppermost Arginine in Sliding Helix S4-I Affects Gating of Cardiac Sodium Channel.
Int J Mol Sci
January 2025
Almazov National Medical Research Centre, 197341 St. Petersburg, Russia.
Several mutations of the uppermost arginine, R219, in the voltage-sensing sliding helix S4 of cardiac sodium channel Nav1.5 are reported in the ClinVar databases, but the clinical significance of the respective variants is unknown (VUSs). AlphaFold 3 models predicted a significant downshift of S4 in the R219C VUS.
View Article and Find Full Text PDFSingle-Template Molecularly Imprinted Chiral Sensor for Enantioselective Recognition of Various Chiral Amino Acids Based on a Dummy Template Strategy.
Anal Chem
January 2025
Jiangsu Key Laboratory of Advanced Catalytic Materials and Technology, School of Petrochemical Engineering, Changzhou University, Changzhou 213164, China.
Designing single-template molecularly imprinted chiral sensors for the enantioselective recognition of various chiral amino acids (AAs) is of great importance for chiral analysis. Here, a dummy template-based chiral sensor is developed by using l-alanine (l-Ala) as the dummy template and poly(-phenylenediamine) as the imprinting layer, which can be used for the enantioselective recognition of various chiral AAs such as Ala, tryptophan (Trp), tyrosine (Tyr), cysteine (Cys), and arginine (Arg). Compared with conventional single-template molecularly imprinted chiral sensors, the designed single-template chiral sensor shows great universality for the recognition of chiral AAs since all chiral AAs possess an Ala-analogous segment.
View Article and Find Full Text PDFFrom Antibacterial Activity to Molecular Mechanism: Case Study of Hexapeptide RWWRWW and Its Analogues.
Chembiochem
January 2025
Southeast University, School of Biological Science and Medical Engineering, 2 Sipailou, Xuanwu District, 210096, Nanjing, CHINA.
In recent years, antimicrobial peptides (AMPs) have emerged as a potent weapon against the growing threat of antibiotic resistance. Among AMPs, the ones containing tryptophan (W) and arginine (R) exhibit enhanced antimicrobial properties, benefiting from the unique physicochemical features of the two amino acids. Herein, we designed three hexapeptides, including WR, DWR (D-isomer), and RF, derived from the original sequence, RWWRWW-NH2 (RW).
View Article and Find Full Text PDFTowards Improved Peptidic α-Ketoamide Inhibitors of the Plasmodial Subtilisin-Like SUB1: Exploration of N-Terminal Extensions and Cyclic Constraints.
ChemMedChem
January 2025
Université de Montpellier: Universite de Montpellier, IBMM, Pôle Chimie Balard, Campus CNRS, 34093, Montpellier, FRANCE.
After more than 15 years of decline, the Malaria epidemy has increased again since 2017, reinforcing the need to identify drug candidates active on new targets involved in at least two biological stages of the Plasmodium life cycle. The SUB1 protease, which is essential for parasite egress in both hepatic and blood stages, would meet these criteria. We previously reported the structure-activity relationship analysis of α-ketoamide-containing inhibitors encompassing positions P4-P2'.
View Article and Find Full Text PDFStructural basis of nucleosome recognition by the conserved Dsup and HMGN nucleosome-binding motif.
bioRxiv
January 2025
Department of Cellular and Molecular Medicine, University of California San Diego, La Jolla, CA, USA.
The tardigrade Dsup and vertebrate high mobility group N (HMGN) proteins bind specifically to nucleosomes via a conserved motif whose structure has not been experimentally determined. Here we used cryo-EM to show that both proteins bind to the nucleosome acidic patch via analogous arginine anchors with one molecule bound to each face of the nucleosome. We additionally employed the natural promoter-containing 5S rDNA sequence for structural analysis of the nucleosome.
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