{"doi":"10.1016/j.str.2017.03.014","title":"X-Ray Crystallography and Electron Microscopy of Cross- and Multi-Module Nonribosomal Peptide Synthetase Proteins Reveal a Flexible Architecture","abstract":null,"journal":"Structure","year":2017,"id":674121,"datarank":0.692268077526189,"base_score":4.61512051684126,"endowment":4.61512051684126,"self_citation_contribution":0.692268077526189,"citation_network_contribution":0.0,"self_endowment_contribution":0.692268077526189,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":100,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"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":695775,"name":"Asfarul S. Haque","orcid":null,"position":1,"is_corresponding":false},{"id":880805,"name":"Khanh Huy Bui","orcid":"0000-0003-2814-9889","position":2,"is_corresponding":false},{"id":1689954,"name":"T. Martin Schmeing","orcid":null,"position":3,"is_corresponding":false},{"id":1761316,"name":"Michael J. Tarry","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"X-Ray Crystallography and Electron Microscopy of Cross- and Multi-Module Nonribosomal Peptide Synthetase Proteins Reveal a Flexible Architecture","abstract":"Nonribosomal peptide synthetases (NRPS) are macromolecular machines that produce peptides with diverse activities. Structural information exists for domains, didomains, and even modules, but little is known about higher-order organization. We performed a multi-technique study on constructs from the dimodular NRPS DhbF. We determined a crystal structure of a cross-module construct including the adenylation (A) and peptidyl carrier protein (PCP) domains from module 1 and the condensation domain from module 2, complexed with an adenosine-vinylsulfonamide inhibitor and an MbtH-like protein (MLP). The action of the inhibitor and the role of the MLP were investigated using adenylation reactions and isothermal titration calorimetry. In the structure, the PCP and A domains adopt a novel conformation, and noncovalent, cross-module interactions are limited. We calculated envelopes of dimodular DhbF using negative-stain electron microscopy. The data show large conformational variability between modules. Together, our results suggest that NRPSs lack a uniform, rigid supermodular architecture.","is_dataset_classified":null,"base_score":4.61512051684126,"endowment":4.61512051684126,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"28434915","pmcid":null,"openalex_id":"https://openalex.org/W2606641580","authors":[],"funders":[{"funder_name":"Canadian Institutes of Health Research","grant_id":"FDN-148472","title":null},{"funder_name":"Merck Sharpe & Dohme","grant_id":"238371","title":null},{"funder_name":"Canadian Institutes of Health Research","grant_id":"unidentified","title":"unidentified"},{"funder_name":"McGill Faculty of Medicine","grant_id":"","title":null},{"funder_name":"Canada Research Chairs","grant_id":"","title":null},{"funder_name":"GRASP","grant_id":"","title":null}],"total_grants":6,"fwci":9.7104,"citation_percentile":0.98773127,"influential_citations":0,"citation_trend":[{"year":2017,"count":8},{"year":2018,"count":17},{"year":2019,"count":14},{"year":2020,"count":11},{"year":2021,"count":13},{"year":2022,"count":13},{"year":2023,"count":7},{"year":2024,"count":8},{"year":2025,"count":7},{"year":2026,"count":1}],"oa_status":"bronze","license":"Elsevier Non-Commercial","oa_locations":[{"url":"http://www.cell.com/article/S0969212617300746/pdf","host_type":"journal"},{"url":"http://www.cell.com/article/S0969212617300746/pdf","host_type":"publisher"},{"url":"https://api.elsevier.com/content/article/PII:S0969212617300746?httpAccept=text/xml","host_type":"publisher"},{"url":"https://api.elsevier.com/content/article/PII:S0969212617300746?httpAccept=text/plain","host_type":"publisher"},{"url":"https://doi.org/10.1016/j.str.2017.03.014","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/28434915","host_type":"repository"},{"url":"https://dx.doi.org/10.1016/j.str.2017.03.014","host_type":""}],"fields_of_study":["Microbial Natural Products and Biosynthesis","Biochemical and Structural Characterization","RNA and protein synthesis mechanisms","0301 basic medicine","0303 health sciences","03 medical and health sciences","Bacteria","Bacterial Proteins","Binding Sites","Enzyme Inhibitors","Peptide Synthases","Protein Binding","Sulfonamides","Vinyl Compounds"],"mesh_terms":["Bacteria","Bacterial Proteins","Binding Sites","Enzyme Inhibitors","Peptide Synthases","Protein Binding","Sulfonamides","Vinyl Compounds"],"keywords":["Nonribosomal peptide","Adenylylation","Isothermal titration calorimetry","Architecture domain","Peptide","Crystallography","Protein structure","Chemistry","Stereochemistry","Biochemistry","Enzyme","Biosynthesis","Materials science","X-ray crystallography","Conformational flexibility","Nonribosomal peptide synthetase","Single-particle Electron Microscopy","Nrps","Mega-enzyme","Mbth-like Protein","Adenosine-vinylsulfonamide Inhibitor","Adenylation Activity","Synthetic Cycle","Sulfonamides","Binding Sites","Vinyl Compounds","Bacteria","Bacterial Proteins","Enzyme Inhibitors","Peptide Synthases","Protein Binding"],"sdg_mappings":[{"sdg_number":3,"sdg_label":"3. Good health"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-16T15:40:36.265258Z","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":[]}