{"doi":"10.1101/2023.07.14.549078","title":"Crystal Structure of the 4-Hydroxybutyryl-CoA Synthetase (ADP-forming) from Nitrosopumilus maritimus","abstract":"Abstract The 3-hydroxypropionate/4-hydroxybutyrate (3HP/4HB) cycle from ammonia-oxidizing Thaumarchaeota is currently considered the most energy-efficient aerobic carbon fixation pathway. The Nitrosopumilus maritimus 4-hydroxybutyryl-CoA synthetase (ADP-forming; Nmar_0206) represents one of several enzymes from this cycle that exhibit increased efficiency over crenarchaeal counterparts. This enzyme reduces energy requirements on the cell, reflecting thaumarchaeal success in adapting to low-nutrient environments. Here we show the structure of Nmar_0206 from Nitrosopumilus maritimus SCM1, which reveals a highly conserved interdomain linker loop between the CoA-binding and ATP-grasp domains. Phylogenetic analysis suggests the widespread prevalence of this loop and highlights both its underrepresentation within the PDB and structural importance within the (ATP-forming) acyl- CoA synthetase (ACD) superfamily. This linker is shown to have a possible influence on conserved interface interactions between domains, thereby influencing homodimer stability. These results provide a structural basis for the energy efficiency of this key enzyme in the modified 3HP/4HB cycle of Thaumarchaeota.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2023,"id":400118,"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":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9506,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":94784,"name":"Bradley B. Tolar","orcid":"0000-0003-0493-1470","position":1,"is_corresponding":false},{"id":1176418,"name":"Bilge Tosun","orcid":"0000-0001-5131-6361","position":2,"is_corresponding":false},{"id":548304,"name":"Yasuo Yoshikuni","orcid":"0000-0002-8372-640X","position":3,"is_corresponding":false},{"id":556947,"name":"Christopher Francis","orcid":"0000-0001-7557-631X","position":4,"is_corresponding":false},{"id":271805,"name":"Soichi Wakatsuki","orcid":"0000-0001-5896-7968","position":5,"is_corresponding":false},{"id":404743,"name":"Hasan DeMi̇rci̇","orcid":"0000-0002-9135-5397","position":6,"is_corresponding":false},{"id":896378,"name":"J Austin Johnson","orcid":"0000-0002-8553-2465","position":0,"is_corresponding":true}],"reference_count":45,"raw_metadata":null,"created_at":"2026-07-19T01:20:00.023537Z","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":[]}