9Q3K

Structure of LarA-like nickel-pincer nucleotide cofactor-utilizing enzyme with a single catalytic histidine residue from Streptococcus plurextorum

Summary for 9Q3K

• Entry DOI: 10.2210/pdb9q3k/pdb
• EMDB information: 72200
• Descriptor: LarA-like nickel-pincer nucleotide cofactor-utilizing enzyme, NICKEL (II) ION, 3-methanethioyl-1-(5-O-phosphono-beta-D-ribofuranosyl)-5-(sulfanylcarbonyl)pyridin-1-ium (3 entities in total)
• Functional Keywords: racemase and epimerase activity, acting on hydroxy acids and derivatives, metal ion binding, catalytic activity, isomerase
• Biological source: Streptococcus plurextorum
• Total number of polymer chains: 8
• Total formula weight: 454354.96

Authors

Subramanian, S.,Gatreddi, S.,Hausinger, R.P.,Hu, J.,Parent, K.N. (deposition date: 2025-08-18, release date: 2025-09-24)

Primary citation

Gatreddi, S.,Subramanian, S.,Sui, D.,Wang, T.,Urdiain-Arraiza, J.,Desguin, B.,Hausinger, R.P.,Parent, K.N.,Hu, J.
Structures of two LarA-like nickel-pincer nucleotide cofactor-utilizing enzymes with a single catalytic histidine residue.
Biorxiv, 2025

PubMed 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 process substrates differently from those of the well-studied LarAHs. Genomic context analysis suggested their potential involvement in carbohydrate metabolism. Together, these findings lay the groundwork for expanding the breadth of reactions and the range of mechanisms of LarA enzymes.

PubMed: 40894700
DOI: 10.1101/2025.08.19.671153

Experimental method

ELECTRON MICROSCOPY (2.2 Å)