9F7E

CtdA Canavanine tRNA-editing deacetylase from Pseudomonas canavaninivorans

Summary for 9F7E

• Entry DOI: 10.2210/pdb9f7e/pdb
• Descriptor: CtdA Canavanyl tRNA Deacylase, SULFATE ION (3 entities in total)
• Functional Keywords: editing, canavanine, arginine, trna editing, b3/b4 domain family, trna binding, rna binding protein
• Biological source: Pseudomonas canavaninivorans
• Total number of polymer chains: 2
• Total formula weight: 50293.03

Authors

Tabagari, N.,Mayans, O. (deposition date: 2024-05-03, release date: 2025-05-14, Last modification date: 2025-11-26)

Primary citation

Tabagari, N.,Hauth, F.,Fleming, J.R.,Hartig, J.S.,Mayans, O.
Indel-driven evolution of the canavanine tRNA-editing deacetylase enzyme CtdA.
J Struct Biol X, 12:100132-100132, 2025

PubMed Abstract: Proteins are heteropolymers composed of twenty standard amino acids, but over 500 non-proteogenic amino acids exist in nature that can be misincorporated into proteins. Canavanine is an antimetabolite of the chemically similar L-arginine. It can be utilized by bacteria such as in the legume rhizome as a sole source of carbon and nitrogen. However, canavanine misincorporates in proteins of this bacterium as its arginyl-tRNA synthetase loads tRNA with both canavanine and arginine. Canavanyl-tRNA deacetylase (CtdA) removes canavanine from misloaded tRNA, preventing its protein toxicity, being the first enzyme known to edit tRNA mischarged with a non-proteinogenic amino acid. We have elucidated CtdA's crystal structure and studied its active site using site-directed mutagenesis. We found that CtdA is a small monomeric enzyme with a central, deep cavity that predictably is the canavanine binding site and a positively charged surface area that likely coordinates the CCA-3' tRNA attachment sequence. CtdA is distantly related to the B3/B4 -editing domains of the multi-subunit enzyme Phenylalanine-tRNA-Synthetase (PheRS). CdtA and B3/B4 domains from bacterial and archaeal/eukaryotic origin are three subclasses of a conserved 3D-fold that differ in type-specific indels, which shape the substrate binding site. We propose a class-unifying nomenclature of secondary structure for this fold. In CtdA, residues Y104, N105, E118 and E191 are relevant for catalysis, of which N105 is conserved in bacterial B3/B4 domains. Residue N105 is in proximity of the canavanyl-ribose junction and might coordinate the nucleophilic water molecule that attacks the substrate, possibly sharing a mechanistic role in CtdA and bacterial B3/B4 editing enzymes.

PubMed: 40687620
DOI: 10.1016/j.yjsbx.2025.100132

Experimental method

X-RAY DIFFRACTION (1.5 Å)