{"doi":"10.1074/jbc.m802168200","title":"Protein-Protein Docking and Analysis Reveal That Two Homologous Bacterial Adenylyl Cyclase Toxins Interact with Calmodulin Differently","abstract":null,"journal":"Journal of Biological Chemistry","year":2008,"id":647790,"datarank":1.4075979955269244,"base_score":3.5263605246161616,"endowment":3.5263605246161616,"self_citation_contribution":0.5289540786924243,"citation_network_contribution":0.8786439168345,"self_endowment_contribution":0.5289540786924243,"citer_contribution":0.8786439168345,"corpus_percentile":null,"corpus_rank":null,"citation_count":33,"citer_count":29,"citers_with_citation_signal":22,"citers_with_endowment":22,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1687907,"name":"Justin E. Jureller","orcid":null,"position":1,"is_corresponding":false},{"id":871177,"name":"Julia T. Warren","orcid":"0000-0003-2017-6444","position":2,"is_corresponding":false},{"id":1687909,"name":"Elena Solomaha","orcid":null,"position":3,"is_corresponding":false},{"id":1687912,"name":"Jan Florián","orcid":null,"position":4,"is_corresponding":false},{"id":1466486,"name":"Wei-Jen Tang","orcid":null,"position":5,"is_corresponding":false},{"id":618477,"name":"Qing Guo","orcid":"0000-0002-3251-508X","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Protein-Protein Docking and Analysis Reveal That Two Homologous Bacterial Adenylyl Cyclase Toxins Interact with Calmodulin Differently","abstract":"Calmodulin (CaM), a eukaryotic calcium sensor that regulates diverse biological activities, consists of N- and C-terminal globular domains (N-CaM and C-CaM, respectively). CaM serves as the activator of CyaA, a 188-kDa adenylyl cyclase toxin secreted by Bordetella pertussis, which is the etiologic agent for whooping cough. Upon insertion of the N-terminal adenylyl cyclase domain (ACD) of CyaA to its targeted eukaryotic cells, CaM binds to this domain tightly ( approximately 200 pm affinity). This interaction activates the adenylyl cyclase activity of CyaA, leading to a rise in intracellular cAMP levels to disrupt normal cellular signaling. We recently solved the structure of CyaA-ACD in complex with C-CaM to elucidate the mechanism of catalytic activation. However, the structure of the interface between N-CaM and CyaA, the formation of which contributes a 400-fold increase of binding affinity between CyaA and CaM, remains elusive. Here, we used site-directed mutations and molecular dynamic simulations to generate several working models of CaM-bound CyaA-ACD. The validity of these models was evaluated by disulfide bond cross-linking, point mutations, and fluorescence resonance energy transfer experiments. Our study reveals that a beta-hairpin region (amino acids 259-273) of CyaA-ACD likely makes contacts with the second calcium binding motif of the extended CaM. This mode of interaction differs from the interaction of N-CaM with anthrax edema factor, which binds N-CaM via its helical domain. Thus, two structurally conserved, bacterial adenylyl cyclase toxins have evolved to utilize distinct binding surfaces and modes of activation in their interaction with CaM, a highly conserved eukaryotic signaling protein.","is_dataset_classified":null,"base_score":3.5263605246161616,"endowment":3.5263605246161616,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"18583346","pmcid":"PMC2527102","openalex_id":"https://openalex.org/W1967282262","authors":[],"funders":[{"funder_name":"NIGMS NIH HHS","grant_id":"GM 62548","title":null},{"funder_name":"NIGMS NIH HHS","grant_id":"R01 GM062548","title":null},{"funder_name":"Howard Hughes Medical Institute","grant_id":"","title":null}],"total_grants":3,"fwci":1.4642,"citation_percentile":0.82361925,"influential_citations":0,"citation_trend":[{"year":2012,"count":4},{"year":2013,"count":3},{"year":2014,"count":3},{"year":2015,"count":1},{"year":2016,"count":2},{"year":2017,"count":3},{"year":2018,"count":1},{"year":2019,"count":2},{"year":2020,"count":1},{"year":2023,"count":1},{"year":2024,"count":2},{"year":2025,"count":2}],"oa_status":"hybrid","license":"cc-by","oa_locations":[{"url":"http://www.jbc.org/article/S002192581949296X/pdf","host_type":"journal"},{"url":"http://www.jbc.org/article/S002192581949296X/pdf","host_type":"publisher"},{"url":"https://api.elsevier.com/content/article/PII:S002192581949296X?httpAccept=text/xml","host_type":"publisher"},{"url":"https://api.elsevier.com/content/article/PII:S002192581949296X?httpAccept=text/plain","host_type":"publisher"},{"url":"https://syndication.highwire.org/content/doi/10.1074/jbc.M802168200","host_type":"publisher"},{"url":"https://doi.org/10.1074/jbc.m802168200","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/18583346","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/2527102","host_type":"repository"}],"fields_of_study":["Bacterial Genetics and Biotechnology","Protein Structure and Dynamics","RNA and protein synthesis mechanisms"],"mesh_terms":["Antigens, Bacterial","Bacillus anthracis","Bacterial Toxins","Bordetella pertussis","Calmodulin","Humans","Protein Binding","Species Specificity","Mutagenesis, Site-Directed","Protein Structure, Tertiary","Mutation, Missense","Enzyme Activators","Protein Structure, Quaternary","Adenylate Cyclase Toxin"],"keywords":["Adenylyl cyclase","Calmodulin","ADCY9","Docking (animal)","Heterotetramer","Biochemistry","Chemistry","ADCY10","Cell biology","Biology","Biophysics","Signal transduction","Enzyme","Gene"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Affordable and clean energy"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[{"name":"pdb"}],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-10T01:53:01.313800Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}