{"doi":"10.1016/j.jbc.2021.100746","title":"From structure to the dynamic regulation of a molecular switch: A journey over 3 decades","abstract":"It is difficult to imagine where the signaling community would be today without the Protein Data Bank. This visionary resource, established in the 1970s, has been an essential partner for sharing information between academics and industry for over 3 decades. We describe here the history of our journey with the protein kinases using cAMP-dependent protein kinase as a prototype. We summarize what we have learned since the first structure, published in 1991, why our journey is still ongoing, and why it has been essential to share our structural information. For regulation of kinase activity, we focus on the cAMP-binding protein kinase regulatory subunits. By exploring full-length macromolecular complexes, we discovered not only allostery but also an essential motif originally attributed to crystal packing. Massive genomic data on disease mutations allows us to now revisit crystal packing as a treasure chest of possible protein:protein interfaces where the biological significance and disease relevance can be validated. It provides a new window into exploring dynamic intrinsically disordered regions that previously were deleted, ignored, or attributed to crystal packing. Merging of crystallography with cryo-electron microscopy, cryo-electron tomography, NMR, and millisecond molecular dynamics simulations is opening a new world for the signaling community where those structure coordinates, deposited in the Protein Data Bank, are just a starting point! It is difficult to imagine where the signaling community would be today without the Protein Data Bank. This visionary resource, established in the 1970s, has been an essential partner for sharing information between academics and industry for over 3 decades. We describe here the history of our journey with the protein kinases using cAMP-dependent protein kinase as a prototype. We summarize what we have learned since the first structure, published in 1991, why our journey is still ongoing, and why it has been essential to share our structural information. For regulation of kinase activity, we focus on the cAMP-binding protein kinase regulatory subunits. By exploring full-length macromolecular complexes, we discovered not only allostery but also an essential motif originally attributed to crystal packing. Massive genomic data on disease mutations allows us to now revisit crystal packing as a treasure chest of possible protein:protein interfaces where the biological significance and disease relevance can be validated. It provides a new window into exploring dynamic intrinsically disordered regions that previously were deleted, ignored, or attributed to crystal packing. Merging of crystallography with cryo-electron microscopy, cryo-electron tomography, NMR, and millisecond molecular dynamics simulations is opening a new world for the signaling community where those structure coordinates, deposited in the Protein Data Bank, are just a starting point! The scientific community is enormously grateful to the visionary leaders of the early crystallography community who realized how important it would be to have an international resource where all new structures would be deposited and validated. Max Perutz, Michael Rossmann, and Fred Richards were among the early pioneers who championed the PDB concept. In 1971 the Protein Data Bank (PDB) was officially announced in Nature New Biology (1Crystallography: Protein Data Bank.Nat. New Biol. 1971; 233: 223Crossref PubMed Scopus (39) Google Scholar) as a joint venture between Brookhaven National Laboratory under the direction of Walter Hamilton and the Cambridge Crystal Data Center, founded by Olga Kennard, with an initial holding of seven protein structures. Helen Berman, who was also involved with the initial establishment of the PDB, led the transformation of the PDB into a modern, worldwide database in 1998. The determination and dedication of these two pioneering women, along with the visionary leadership of Perutz, Richards, Rossmann, and others, ","journal":"Journal of Biological Chemistry","year":2021,"id":149460,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":106,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.744,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":635994,"name":"Jian Wu","orcid":"0000-0002-8031-9462","position":1,"is_corresponding":false},{"id":637224,"name":"Jessica Bruystens","orcid":null,"position":2,"is_corresponding":false},{"id":79813,"name":"Jason C. Del Rio","orcid":"0000-0001-8540-2065","position":3,"is_corresponding":false},{"id":510677,"name":"Tsan‐Wen Lu","orcid":null,"position":4,"is_corresponding":false},{"id":381183,"name":"Alexandr P. Kornev","orcid":"0000-0002-1543-3795","position":5,"is_corresponding":false},{"id":635995,"name":"Lynn F. Ten Eyck","orcid":"0000-0002-4562-9027","position":6,"is_corresponding":false},{"id":232971,"name":"Susan S. Taylor","orcid":"0000-0002-7702-6108","position":0,"is_corresponding":true}],"reference_count":62,"raw_metadata":null,"created_at":"2026-07-18T23:42:56.251607Z","pmid":"33957122","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":[]}