The sodium efflux pump ATP4 is a leading antimalarial target, but suffers from a lack of high-resolution structural information needed to identify functionally important features in conserved regions and guide rational design of next generation inhibitors. Here, we determine a 3.7Å cryoEM structure of ATP4 purified from CRISPR-engineered parasites, revealing a previously unknown, apicomplexan-specific binding partner, ABP, which forms a conserved, likely modulatory interaction with ATP4. The discovery of ABP presents a new avenue for designing novel ATP4 inhibitors.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11888398 | PMC |
| http://dx.doi.org/10.1101/2025.02.25.640208 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Targeting Blood-Stage Malaria: Design, Synthesis, Characterization, In Vitro, and In Silico Evaluation of Pyrrolidinodiazenyl Chalcones.
Chem Biol Drug Des
March 2025
Department of Chemistry, Pondicherry University, Kalapet, Puducherry, India.
Malaria is a pervasive and deadly threat to the global population, and the resources available to treat this disease are limited. There is widespread clinical resistance to the most commonly prescribed antimalarial drugs. To address this issue, we synthesized a range of 4'-pyrrolidinodiazenyl chalcones using a covalent bitherapy approach to study their potential antimalarial properties.
View Article and Find Full Text PDFRevisiting the druggable genome using predicted structures and data mining.
NPJ Drug Discov
March 2025
Department of Pediatrics, University of California, San Diego, La Jolla, CA USA.
Identification of novel drug targets is a key component of modern drug discovery. While antimalarial targets are often identified through the mechanism of action studies on phenotypically derived inhibitors, this method tends to be time- and resource-consuming. The discoverable target space is also constrained by existing compound libraries and phenotypic assay conditions.
View Article and Find Full Text PDFThe sodium efflux pump ATP4 is a leading antimalarial target, but suffers from a lack of high-resolution structural information needed to identify functionally important features in conserved regions and guide rational design of next generation inhibitors. Here, we determine a 3.7Å cryoEM structure of ATP4 purified from CRISPR-engineered parasites, revealing a previously unknown, apicomplexan-specific binding partner, ABP, which forms a conserved, likely modulatory interaction with ATP4.
View Article and Find Full Text PDFCharacterizing Public Sentiments and Drug Interactions in the COVID-19 Pandemic Using Social Media: Natural Language Processing and Network Analysis.
J Med Internet Res
March 2025
School of Public Health, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Background: While the COVID-19 pandemic has induced massive discussion of available medications on social media, traditional studies focused only on limited aspects, such as public opinions, and endured reporting biases, inefficiency, and long collection times.
Objective: Harnessing drug-related data posted on social media in real-time can offer insights into how the pandemic impacts drug use and monitor misinformation. This study aimed to develop a natural language processing (NLP) pipeline tailored for the analysis of social media discourse on COVID-19-related drugs.
Chemical targeting of prolyl-tRNA synthetase stalls ovarian development and kills malaria vectors.
J Infect Dis
March 2025
Molecular Medicine - Structural Parasitology Group, International Center for Genetic Engineering and Biotechnology (ICGEB); Aruna Asaf Ali Marg, New Delhi-110067, India.
Objective: Along with rising resistance to antimalarials, the emergence of insecticide resistance in Anopheles mosquito species also remains a serious concern. Here, we reveal two potent compounds that show larvicidal and endectocidal activity against malaria vectors, Anopheles culicifacies and Anopheles stephensi, respectively.
Methods: We investigated larvicidal activity of two inhibitors against III-instar larvae of Anopheles culicifacies.
Want 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!