Apicomplexan genomes encode multiple pepsin-family aspartyl proteases (APs) that phylogenetically cluster to six independent clades (A to F). Such diversification has been powered by the function-driven evolution of the ancestral apicomplexan AP gene and is associated with the adaptation of various apicomplexan species to different strategies of host infection and transmission through various invertebrate vectors. To estimate the potential roles of APs, we performed qRT-PCR-based expressional profiling of APs (BmASP2, 3, 5, 6), which revealed the dynamically changing mRNA levels and indicated the specific roles of individual BmASP isoenzymes throughout the life cycle of this parasite. To expand on the current knowledge on piroplasmid APs, we searched the EuPathDB and NCBI GenBank databases to identify and phylogenetically analyse the complete sets of APs encoded by the genomes of selected and species. Our results clearly determine the potential roles of identified APs by their phylogenetic relation to their homologues of known function- plasmepsins (PfPM I-X) and aspartyl proteases (TgASP1-7). Due to the analogies with plasmodial plasmepsins, piroplasmid APs represent valuable enzymatic targets that are druggable by small molecule inhibitors-candidate molecules for the yet-missing specific therapy for babesiosis.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8540915 | PMC |
| http://dx.doi.org/10.3390/pathogens10101241 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Weak acid and pepsin reflux induce laryngopharyngeal mucosal barrier injury: A rabbit-model-based study.
PLoS One
January 2025
Department of Otorhinolaryngology, Fujian Provincial Hospital, Fuzhou, Fujian, China.
Objective: Using rabbit models, this study simulated the laryngopharynx's response to the synergistic effects of various acidic reflux environments and pepsin to investigate the response mechanism underlying weak acid reflux and pepsin in the mucosal barrier injury of laryngopharyngeal reflux.
Methods: The rabbits were divided into six groups, and the original larynx was recorded for each group. During the study period, rabbits were sprayed with different doses of acid and pepsin solutions and monitored for hypopharyngeal mucosal transient impedance before and after modeling.
Positively charged cytoplasmic residues in corin prevent signal peptidase cleavage and endoplasmic reticulum retention.
Commun Biol
January 2025
Cyrus Tang Hematology Center, Collaborative Innovation Center of Hematology, State Key Laboratory of Radiation Medicine and Prevention, Suzhou Medical College, Soochow University, Suzhou, 215123, China.
Positively charged residues are commonly located near the cytoplasm-membrane interface, which is known as the positive-inside rule in membrane topology. The mechanism underlying the function of these charged residues remains poorly understood. Herein, we studied the function of cytoplasmic residues in corin, a type II transmembrane serine protease in cardiovascular biology.
View Article and Find Full Text PDFThe renin-angiotensin-aldosterone system and salt sensitivity of blood pressure offer new insights in obesity phenotypes.
Obesity (Silver Spring)
February 2025
Division of Endocrinology, Diabetes and Hypertension, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Objective: Individuals who have metabolically healthy overweight/obesity (MHOO) do not have cardiometabolic complications despite an elevated BMI. Renin-angiotensin-aldosterone system (RAAS) activation and salt sensitivity of blood pressure (SSBP) are cardiovascular disease (CVD) risks, which are increased in individuals with higher BMI values. Little is known about the differences in RAAS activation and SSBP between MHOO and metabolically unhealthy overweight/obesity (MUOO) phenotypes.
View Article and Find Full Text PDFEnhanced sampling of protein conformational changes via true reaction coordinates from energy relaxation.
Nat Commun
January 2025
Center for Bioinformatics and Quantitative Biology, Richard and Loan Hill Department of Biomedical Engineering, The University of Illinois Chicago, 851 South Morgan Street, Chicago, IL, 60607, USA.
The bottleneck in enhanced sampling lies in finding collective variables that effectively accelerate protein conformational changes; true reaction coordinates that accurately predict the committor are the well-recognized optimal choice. However, identifying them requires unbiased natural reactive trajectories, which, paradoxically, require effective enhanced sampling. Using the generalized work functional method, we uncover that true reaction coordinates control both conformational changes and energy relaxation, enabling us to compute them from energy relaxation simulations.
View Article and Find Full Text PDFHIV OctaScanner: A Machine Learning Approach to Unveil Proteolytic Cleavage Dynamics in HIV-1 Protease Substrates.
J Chem Inf Model
January 2025
State Key Laboratory of Microbial Metabolism, Joint International Research Laboratory of Metabolic & Developmental Sciences and School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai 200030, P.R. China.
The rise of resistance to antiretroviral drugs due to mutations in human immunodeficiency virus-1 (HIV-1) protease is a major obstacle to effective treatment. These mutations alter the drug-binding pocket of the protease and reduce the drug efficacy by disrupting interactions with inhibitors. Traditional methods, such as biochemical assays and structural biology, are crucial for studying enzyme function but are time-consuming and labor-intensive.
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!