Envenoming by snakebite is an important global health issue that has received little attention, leading the World Health Organization to naming it as neglected tropical disease. Several snakebites present serious local symptoms manifested on victims that may not be efficiently neutralized by serum therapy. Phospholipase A-like (PLA-like) toxins are present in Viperidae venoms and are responsible for local myotoxic activity. Herein, we investigated the association between BthTX-I toxin and caftaric acid (CFT), a molecule present in plants. CFT neutralized neuromuscular blocking and muscle-damaging activities promoted by BthTX-I. Calorimetric and light-scattering assays demonstrated that CFT inhibitor interacted with dimeric BthTX-I. Bioinformatics simulations indicated that CFT inhibitor binds to the toxin's hydrophobic channel (HCh). According to the current myotoxic mechanism, three different regions of PLA-like toxins have specific tasks: protein allosteric activation (HCh), membrane dockage (MDoS), and membrane rupture (MDiS). We propose CFT inhibitor interferes with the allosteric activation, which is related to the conformation change leading to the exposure/alignment of MDoS/MDiS region. This is the first report of a PLA-like toxin fully inhibited by a compound that interacts only with its HCh region. Thus, CFT is a novel candidate to complement serum therapy and improve the treatment of snakebite.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.biochi.2020.01.010 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Genomic analysis of comprehensive next generation sequencing data to explore the criteria for MET amplification as an actionable biomarker in NSCLC.
Lung Cancer
January 2025
Division of Medical Oncology, Department of Medicine, University of Colorado School of Medicine, Aurora, CO 80045, USA.
Introduction: MET amplification (METamp) can be a de novo or acquired resistance driver; however, the definition of METamp that best captures patients who may respond to targeted therapy remains debated. We explored the genomic landscape of METamp NSCLC including degree of amplification, co-drivers, amplicon size, and outcomes to MET inhibitors.
Methods: Hybrid-capture NGS-based genomic profiling from 88,547 tissue and 12,428 liquid NSCLC samples were queried for METamp (copy number (CN) ≥ ploidy + 4, or amplification ratio (AmpRatio; [CN/sample ploidy] ≥ 3).
Changes in Aqueous Angiopoietin-1/2 Concentrations During the Induction Phase of Intravitreal Faricimab Injections for Diabetic Macular Edema.
Transl Vis Sci Technol
December 2024
Kawasaki-Tama Eye Clinic, Kawasaki, Kanagawa, Japan.
Purpose: The purpose of this study was to investigate the dynamic changes in aqueous concentrations of angiopoietin (Ang)-1/2 and vascular endothelial growth factor (VEGF) during injection in treatment-naïve patients with diabetic macular edema (DME) receiving faricimab during the induction phase (3 consecutive monthly doses) and retrospectively analyze the data.
Methods: Thirty-five eyes of 26 patients (age = 63.1 ± 12.
The analysis of foveal microvascular anomalies in retinopathy of prematurity after anti-vascular endothelial growth factor therapy using optical coherence tomography angiography.
BMC Ophthalmol
November 2024
Department of Ophthalmology, Peking University People's Hospital, Eye Disease and Optometry Institute, Beijing Key Laboratory of Diagnosis and Therapy of Retinal and Choroid Diseases, College of Optometry, Peking University Health Science Center, No. 11 Xizhimen South Street, Xicheng District, Beijing, China.
Background: To investigate the quantitative vascular and structural differences in the foveal region of the eyes in retinopathy of prematurity children with or without anti-vascular endothelial growth factor (VEGF) therapy and healthy children using optical coherence tomography angiography (OCTA).
Methods: This cross-sectional study analyzed 75 eyes from 44 subjects, categorized into four groups: ROP children treated with Conbercept or Ranibizumab, spontaneously regressed ROP, and healthy age-matched children. Using spectral-domain OCT and OCTA, we assessed parameters like central foveal thickness (CFT), foveal avascular zone (FAZ), superficial/deep capillary plexus (SCP/DCP), and choroidal vessel density (VD) at the fovea.
Structure of the human dopamine transporter and mechanisms of inhibition.
Nature
August 2024
Vollum Institute, Oregon Health and Science University, Portland, OR, USA.
The neurotransmitter dopamine has central roles in mood, appetite, arousal and movement. Despite its importance in brain physiology and function, and as a target for illicit and therapeutic drugs, the human dopamine transporter (hDAT) and mechanisms by which it is inhibited by small molecules and Zn are without a high-resolution structural context. Here we determine the structure of hDAT in a tripartite complex with the competitive inhibitor and cocaine analogue, (-)-2-β-carbomethoxy-3-β-(4-fluorophenyl)tropane (β-CFT), the non-competitive inhibitor MRS7292 and Zn (ref.
View Article and Find Full Text PDFFactors Contributing to Coronary Microvascular Dysfunction in Patients with Angina and Non-Obstructive Coronary Artery Disease.
J Cardiovasc Dev Dis
July 2024
Department of Cardiovascular Medicine, JR Hiroshima Hospital, 3-1-36, Futabanosato, Higashi-Ku, Hiroshima 732-0057, Japan.
Background: Coronary microvascular dysfunction (CMD), characterised by a reduced coronary flow reserve (CFR) or an increased index of microcirculatory resistance (IMR), has received considerable attention as a cause of chest pain in recent years. However, the risks and causes of CMD remain unclear; therefore, effective treatment strategies have not yet been established. Heart failure or coronary artery disease (CAD) is a risk factor for CMD, with a higher prevalence among women.
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!