The DOI matches its Crossref record; 51 of the 51 references it cites were found in a registry or an index.
Structural basis for the activation of anthrax adenylyl cyclase exotoxin by calmodulin
Abstract
Oedema factor, a calmodulin-activated adenylyl cyclase, is important in the pathogenesis of anthrax. Here we report the X-ray structures of oedema factor with and without bound calmodulin. Oedema factor shares no significant structural homology with mammalian adenylyl cyclases or other proteins. In the active site, 3'-deoxy-ATP and a single metal ion are well positioned for catalysis with histidine 351 as the catalytic base. This mechanism differs from the mechanism of two-metal-ion catalysis proposed for mammalian adenylyl cyclases. Four discrete regions of oedema factor form a surface that recognizes an extended conformation of calmodulin, which is very different from the collapsed conformation observed in other structures of calmodulin bound to effector peptides. On calmodulin binding, an oedema factor helical domain of relative molecular mass 15,000 undergoes a 15 A translation and a 30 degrees rotation away from the oedema factor catalytic core, which stabilizes a disordered loop and leads to enzyme activation. These allosteric changes provide the first molecular details of how calmodulin modulates one of its targets.
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“We also found a cluster enriched for the anthrax_toxA Pfam (PF03497; Fig. 5b), more specifically, the annotated domains contained structures similar to the oedema factor, a calmodulin-activated adenylyl cyclase32.”
From Clustering predicted structures at the scale of the known protein universe (2023) · cites this paper as [32]
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BindingDB Entry 50004800: Structure-based redesign of an edema toxin inhibitor.
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Mucosal Immunity Against Anthrax
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Metadata
- Authors
- Drum, C. L., Yan, S.-Z., Bard, J., Shen, Y.-Q., Lu, D., Soelaiman, S., Grabarek, Z., Bohm, A., & Tang, W.-J.
- Affiliations
- University of Chicago (US)
- Boston Biomedical Research Institute (US)
- Tufts University (US)
- Corresponding author
- Tang, Wei-Jen
- Venue
- Nature
- Published
- 2002-01
- Volume
- 415
- Issue
- 6870
- Pages
- 396-402
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W2096942328
- Cited by
- 413
- References
- 51
- Citations by year
- 2025: 4 · 2024: 5 · 2023: 10 · 2022: 11 · 2021: 6 · 2020: 13 · 2019: 12 · 2018: 8 · 2017: 11 · 2016: 12 · 2015: 13 · 2014: 12 · 2013: 14 · 2012: 19
- FWCI
- 12.98
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Funders
- American Cancer Society
- American Heart Association
- National Institutes of Health
- National Institute on Drug Abuse
- National Institute of General Medical Sciences
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bacillus and Francisella bacterial research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Structural Biology › Enzyme Structure and Function
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
- Keywords
- anthrax toxin, adenylate cyclase, calmodulin, enzyme activation, allosteric regulation, calmodulin binding site, metal ion catalysis, protein structure
- MeSH terms
- Adenylyl Cyclases, Amino Acid Sequence, Animals, Antigens, Bacterial, Bacillus anthracis, Bacterial Toxins, Calmodulin, Enzyme Activation, Exotoxins, Humans, Models, Molecular, Molecular Sequence Data, Protein Binding, Protein Conformation, Structure-Activity Relationship, Crystallography, X-Ray, Catalytic Domain, Macromolecular Substances
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