AI Article Synopsis
- The research focuses on overcoming drug resistance in bacteria by targeting a protein called PBP2a, which is used for cell wall biosynthesis even in the presence of antibiotics.
- Nine phenolic compounds from Bergenia species were tested for their ability to interact with the allosteric site of PBP2a, with vitexin emerging as the most effective candidate.
- Binding energy calculations showed that vitexin has a stronger inhibitory effect on PBP2a compared to the control molecule, suggesting it could potentially reduce PBP2a's activity and enhance treatment options for MRSA infections.
Article Abstract
Background: For cell wall biosynthesis, drug-resistant uses a special protein called PBP2a, even when antibiotics are present and stop its natural processes from working. To combat this, novel therapies are required to specifically target PBP2a with greater efficacy.
Methods: Using computational approaches, we screened nine phenolic compounds from other Bergenia species, including , against the PBP2a allosteric site to explore the potential interaction between phenolic compounds and a specific region of PBP2a known as the allosteric site.
Results: Based on interaction patterns and estimated affinity, vitexin has been found to be the most prominent phenolic compound. We performed MD simulations on vitexin and ceftazidime as control molecules based on the docking results. The binding free energy estimates of vitexin (-94.48 +/- 17.92 kJ/mol) using MM/PBSA were lower than those of the control (-67.61 +/- 12.29 kJ/mol), which suggests that vitexin may be able to inhibit PBP2a activity in MRSA.
Conclusion: It has been intriguing to observe a correlation between the affinity of the lead vitexin at the allosteric site and the modification of Tyr446, the active site gatekeeper residue in PBP2a. Our findings have implied that lead vitexin can either directly or indirectly decrease PBP2a activity by inducing allosteric site change in conventional medicine.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.2174/0115680266312143240805191718 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Clinical Manifestations.
Alzheimers Dement
December 2024
Suven Life Sciences, Hyderabad, Telangana, India.
Background: Centrally acting muscarinic acetylcholine receptor antagonists like atropine and scopolamine can induce psychosis-like symptoms. Xanomeline, a muscarinic M1/M4 preferring agonist attenuated the effects of amphetamine (animal model for schizophrenia) in the wild-type mice, however, such effects were absent in muscarinic M4 knockout mice. In addition, xanomeline was also found to be effective in attenuating neuropsychiatric symptoms.
View Article and Find Full Text PDFUnderstanding Folding of bFGF and Potential Cellular Protective Mechanisms of Neural Cells.
Biochemistry
January 2025
Department of Chemical and Biomolecular Engineering, University of Maryland, College Park, Maryland 20742, United States.
Traumatic brain injury (TBI) is a serious health condition that affects an increasing number of people, especially veterans and athletes. TBI causes serious consequences because of its long-lasting impact on the brain and its alarming frequency of occurrence. Although the brain has some natural protective mechanisms, the processes that trigger them are poorly understood.
View Article and Find Full Text PDFNovel Orthosteric/Allosteric Ligands of Cannabinoid Receptors: An Unexpected Pharmacological Profile.
J Med Chem
January 2025
Department of Pharmacy, University of Pisa, 56126 Pisa, Italy.
The design of dualsteric/bitopic receptor ligands as compounds capable of simultaneously interacting with both the orthosteric and an allosteric binding site has gained importance to achieve enhanced receptor specificity and minimize off-target effects. In this work, we reported the synthesis and biological evaluation of a new series of compounds, namely, the series, obtained by chemically combining the CB1R ago-positive allosteric modulators (PAM) with the cannabinoid receptors (CBRs) orthosteric agonist . Therefore, compounds were designed as dualsteric/bitopic ligands for CB1R with the aim of obtaining stronger CB1R agonists or ago-PAMs, with improved receptor subtype selectivity and reduction of central side effects.
View Article and Find Full Text PDFExamining Arginase-1 Trimerization Uncovers a Promising Allosteric Site for Inhibition.
J Med Chem
January 2025
Louvain Drug Research Institute (LDRI), Medicinal Chemistry Research Group (CMFA), Université Catholique de Louvain (UCLouvain), Brussels B-1200, Belgium.
Arginase-1 (ARG-1) is a promising target for cancer immunotherapy, but the small size and the highly polar nature of its catalytic site present significant challenges for inhibitor development. An alternative strategy to induce enzyme inhibition by targeting protein oligomerization has been developed recently, offering several advantages such as increased selectivity, promotion of protein degradation, and potential substoichiometric inhibition. In this study, we demonstrated that only trimeric ARG-1 is active, which was confirmed by producing monomeric arginase-1.
View Article and Find Full Text PDFFunctional dynamics of G protein-coupled receptors reveal new routes for drug discovery.
Nat Rev Drug Discov
January 2025
Euler Institute, Faculty of Biomedical Sciences, Università della Svizzera italiana (USI), Lugano, Switzerland.
G protein-coupled receptors (GPCRs) are the largest human membrane protein family that transduce extracellular signals into cellular responses. They are major pharmacological targets, with approximately 26% of marketed drugs targeting GPCRs, primarily at their orthosteric binding site. Despite their prominence, predicting the pharmacological effects of novel GPCR-targeting drugs remains challenging due to the complex functional dynamics of these receptors.
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!