Download MendeleyCrystal Structure of 3-Hydroxypropionyl-CoA Synthetase (ADP-forming) from Nitrosopumilus maritimus.
Johnson, J., Tosun, B., Yilmaz, M., Tolar, B.B., Yoshikuni, Y., Francis, C.A., Doukov, T., Yokoi, S., Wakatsuki, S., DeMirci, H.(2025) bioRxiv
- PubMed: 41040329
- DOI: https://doi.org/10.1101/2025.09.22.677778
- Primary Citation of Related Structures:
9Y43 - PubMed Abstract:
The 3-hydroxypropionate/4-hydroxybutyrate (3HP/4HB) cycle in thaumarchaeota contributes significantly to global organic carbon fixation as the most energetically efficient aerobic carbon fixation pathway. The thaumarchaeal 3-Hydroxypropionyl-CoA Synthetase (ADP-forming; Nmar_1309) is crucial to this efficiency, utilizing ATP to ADP catalysis. This first reported structure of Nmar_1309 reveals a homodimer with a unique subdomain organization ([3-4-1-2-5]) and a distinct linker between subdomains 4 and 1. The presence of bound substrates including 3-hydroxypropionate, non-hydrolyzable ATP (ADPNP), and a phosphate suggests an intermediate state mimicking a reaction step immediately preceding the formation of a 3-hydroxypropionyl-phosphohistidine. Conformational differences were observed between the two chains of the homodimer, likely influenced by the binding of a single ADPNP molecule in one chain. Phylogenetic analysis suggests that while 4HB synthetases may have evolved earlier in the evolutionary timeline, 3HP synthetases in Thaumarchaeota may have occurred after the Great Oxygenation Event. These structural data provide further characterization of the 3HP/4HB cycle and, in conjunction with the structure of 4-hydroxybutyryl-CoA synthetase, Nmar_0206, provide baseline structures of the key ADP-forming Acyl-CoA synthetases within this pathway.
