Structures of two LarA-like nickel-pincer nucleotide cofactor-utilizing enzymes with a single catalytic histidine residue.

ABSTRACT: The nickel pincer nucleotide (NPN) cofactor catalyzes the racemization/epimerization of α-hydroxy acids in enzymes of the LarA family. The established proton-coupled hydride transfer mechanism requires two catalytic histidine residues that alternately act as general acids and general bases. Notably, however, a fraction of LarA homologs (LarAHs) lack one of the active site histidine residues, replacing it with an asparaginyl side chain that cannot participate in acid/base catalysis. Here, we investigated two such LarAHs and solved their cryo-electron microscopic structures with and without loaded NPN cofactor, respectively. The structures revealed a consistent octameric assembly that is unprecedented in the LarA family and unveiled a new set of active site residues that likely recognize and

SUBMITTER: Gatreddi S 

PROVIDER: S-EPMC12393405 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature