{"doi":"10.1073/pnas.2507700122","title":"An unusual Co–S bond links B <sub>12</sub> chaperones in an interprotein complex","abstract":"Chaperones in trafficking pathways ensure specificity of transition metal loading and protection against adventitious side reactions. In B 12 , an essential cofactor for humans, a cobalt ion is coordinated to a &gt;1.3 kDa tetrapyrrolic scaffold, posing logistical challenges for its translocation. In this study, we report the 3.4 Å crystal structure of the human MMACHC and MMADHC B 12 chaperones, tethered via a rarely seen covalent cobalt–sulfur bond. B 12 is bound in the base-off state to MMACHC, with Cys-261 on MMADHC serving as the upper axial ligand; the lower-axial position is vacant. The propensity of thiolato-cobalamin derivatives bound to MMACHC to undergo spontaneous decomposition via general acid catalysis or reduction/oxidation chemistry is averted in the interprotein complex with MMADHC. An exposed face in the complex suggests an exit route for B 12 . No known clinical variants localize to the interprotein interface, consistent with the cobalt–sulfur bond being key to forming the high-affinity complex.","journal":"Proceedings of the National Academy of Sciences","year":2025,"id":524511,"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":4,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9544,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":495543,"name":"Markus Ruetz","orcid":"0000-0001-9540-7310","position":1,"is_corresponding":false},{"id":1074318,"name":"Natalie Heitman","orcid":null,"position":2,"is_corresponding":false},{"id":702372,"name":"Ryan Hall","orcid":"0000-0003-2674-7834","position":3,"is_corresponding":false},{"id":705258,"name":"Thomas C. Brunold","orcid":"0000-0001-6516-598X","position":4,"is_corresponding":false},{"id":265994,"name":"Ruma Banerjee","orcid":"0000-0001-8332-3275","position":5,"is_corresponding":false},{"id":495542,"name":"Romila Mascarenhas","orcid":"0000-0002-5099-3528","position":0,"is_corresponding":true}],"reference_count":54,"raw_metadata":null,"created_at":"2026-07-19T02:50:12.083054Z","pmid":"40996799","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":[]}