12BK

Moorella thermoacetica LarC (conformation 3)

This is a non-PDB format compatible entry.

Summary for 12BK

• Entry DOI: 10.2210/pdb12bk/pdb
• EMDB information: 76281
• Descriptor: Pyridinium-3,5-bisthiocarboxylic acid mononucleotide nickel insertion protein (1 entity in total)
• Functional Keywords: enzyme, nickel insertase, cyclometalliase, metal binding protein
• Biological source: Moorella thermoacetica (strain ATCC 39073 / JCM 9320)
• Total number of polymer chains: 6
• Total formula weight: 265534.19

Authors

Kim, K.H.,Wolfe, R. (deposition date: 2026-03-25, release date: 2026-07-29, Last modification date: 2026-09-09)

Primary citation

Wolfe, R.,Turmo, A.,Velasquez-Rivertte, S.,Sui, D.,Granados-Villanueva, D.,Desguin, B.,Hu, J.,Hausinger, R.P.,Kim, K.H.
Structural and functional analysis of LarC, a CTP-dependent cyclometallase required for nickel-pincer nucleotide cofactor biosynthesis.
Sci Adv, 12:eaeh6867-eaeh6867, 2026

PubMed Abstract: Biosynthesis of the nickel-pincer mononucleotide metallocofactor requires a CTP-dependent nickel insertion reaction catalyzed by LarC, whose mechanism of C-Ni bond formation is not fully understood. Here, we report the first cryo-electron microscopy structures of full-length LarC from with and without a mimic of the CMPylated reaction intermediate. LarC assembles as a hexamer comprising a central LarC2 domain core and peripheral LarC1 domain trimers connected by long, flexible interdomain linkers. The LarC1 domains contain a conserved histidine-rich region for nickel binding and an adjacent conserved acidic pocket, both essential for activity. Structural modeling suggests that the intermediate binds within the acidic pocket adjacent to the putative nickel-binding site, while cryo-EM density for an intermediate analog identifies an interdomain cleft near the LarC2 CTP-binding site as a likely transfer site. Based on these findings, we propose that the intermediate is transferred through the interdomain cleft from LarC2, where it is CMPylated, to LarC1 for nickel insertion.

PubMed: 42647608
DOI: 10.1126/sciadv.aeh6867

Experimental method

ELECTRON MICROSCOPY (3.87 Å)