Anthrax edema factor (EF) is a key virulence factor secreted by Bacillus anthracis. Here, we report a structure, at 3.0 A resolution, of the catalytic domain of EF (EF3) in complex with calmodulin (CaM) and adenosine 5'-(alpha,beta-methylene)-triphosphate (AMPCPP). Although the binding of the triphosphate of AMPCPP to EF3 can be superimposed on that of previously determined 3'deoxy-ATP (3'dATP) and 2'deoxy 3' anthraniloyl-ATP (2'd3' ANT-ATP) in EF3-CaM, the ribose and the adenine rings of AMPCPP are rotated approximately 105 and 180 degrees, respectively, relative to those of 3'dATP and 2'd3'ANT-ATP. Based on this model, K382 and F586 should play key roles in the recognition of adenine. However, mutations of these residues to alanine either separately or together cause only modest changes in Michaelis-Menten constants and IC50 values of AMPCPP and cAMP. Therefore, this alternate binding mode of the adenosine of AMPCPP binds to EF likely playing only a minor role in ATP binding and in catalysis.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.bbrc.2004.03.046 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Rational corticosteroids administration and antibiotic treatment is key to managing cutaneous anthrax.
BMC Infect Dis
October 2024
Department of Infectious Diseases, General Hospital of Ningxia Medical University, 804 Shengli Street, Xingqing District, Yinchuan, Ningxia, 750004, China.
Background: Anthrax is a global health concern, with cutaneous anthrax accounting for over 95% of cases and generally promising outcomes. Nonetheless, the absence of timely intervention can result in mortality rates of 10-40%. This research aims to explore the clinical presentations and phenotypic characteristics of cutaneous anthrax patients and evaluate the efficacy of various therapeutic approaches.
View Article and Find Full Text PDFA Rare Presentation of Anthrax: A Pediatric Patient with Palpebral Anthrax.
Sisli Etfal Hastan Tip Bul
April 2024
Department of Ophthalmology, Cukurova University Faculty of Medicine, Adana, Türkiye.
Article Synopsis
- Anthrax is a rare disease caused by the bacterium Bacillus anthracis, with cutaneous anthrax being the most common form.
- A case study of a nine-year-old boy with anthrax on his left eyelids showed rapid progression from a papular reaction to necrosis and eschar formation.
- Treatment with antibiotics like ciprofloxacin and clindamycin led to a positive clinical response, highlighting the importance of early diagnosis and treatment to prevent complications like scarring and deformity.
Anthrax Toxin: Model System for Studying Protein Translocation.
J Mol Biol
April 2024
Department of Microbial Pathogenesis, School of Dentistry, University of Maryland, Baltimore, 650 W. Baltimore Street, Baltimore, MD 21201, USA. Electronic address:
Dedicated translocase channels are nanomachines that often, but not always, unfold and translocate proteins through narrow pores across the membrane. Generally, these molecular machines utilize external sources of free energy to drive these reactions, since folded proteins are thermodynamically stable, and once unfolded they contain immense diffusive configurational entropy. To catalyze unfolding and translocate the unfolded state at appreciable timescales, translocase channels often utilize analogous peptide-clamp active sites.
View Article and Find Full Text PDFEarly Circulating Edema Factor in Inhalational Anthrax Infection: Does It Matter?
Microorganisms
January 2024
Département des Maladies Infectieuses, Institut de Recherche Biomédicale des Armées, 91220 Brétigny-sur-Orge, France.
Anthrax toxins are critical virulence factors of and strains that cause anthrax-like disease, composed of a common binding factor, the protective antigen (PA), and two enzymatic proteins, lethal factor (LF) and edema factor (EF). While PA is required for endocytosis and activity of EF and LF, several studies showed that these enzymatic factors disseminate within the body in the absence of PA after intranasal infection. In an effort to understand the impact of EF in the absence of PA, we used a fluorescent EF chimera to facilitate the study of endocytosis in different cell lines.
View Article and Find Full Text PDFDevelopment of a New Cell-Based AP-1 Gene Reporter Potency Assay for Anti-Anthrax Toxin Therapeutics.
Toxins (Basel)
August 2023
Division of Biotechnology Review and Research II, Office of Biotechnology Products, Office of Pharmaceutical Quality, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, MD 20993, USA.
Anthrax toxin is a critical virulence factor of . The toxin comprises protective antigen (PA) and two enzymatic moieties, edema factor (EF) and lethal factor (LF), forming bipartite lethal toxin (LT) and edema toxin (ET). PA binds cellular surface receptors and is required for intracellular translocation of the enzymatic moieties.
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!