Recent Updates on DTD (D-Tyr-tRNATyr Deacylase): An Enzyme Essential for Fidelity and Quality of Protein Synthesis

Abstract

During protein synthesis, there are several checkpoints in the cell to ensure that the information encoded within genetic material is decoded correctly. Charging of tRNA with its cognate amino acid is one of the important steps in protein synthesis and is carried out by aminoacyl-tRNA synthetase (aaRS) with great accuracy. However, due to presence of D-amino acids in the cell, sometimes aaRS charges tRNA with D-amino acids resulting in the hampering of protein translational process, which is lethal to the cell. Every species has some mechanism in order to prevent the formation of D-amino acid-tRNA complex, for instance DTD (D-Tyr-tRNA deacylase) is an enzyme responsible for the cleavage of ester bond formed between D-amino acid and tRNA leading to error free translation process. In this review, structure, function, and enzymatic mechanism of DTD are discussed. The role of DTD as a drug target is also considered.

Symmetry breaking and functional incompleteness in biological systems

“…Both (D)-and (L)-amino acids (DAAs and LAAs, respectively) are synthesized by racemase enzymes and can be found at high concentrations in cells (for more references, see Bhatt, Soni, and Sharma 2016). Since the presence of DAAs can hamper the protein translational process, several cellular mechanisms are dedicated to protecting the process against possible errors in protein synthesis and in its secondary structure.…”

“…Since the presence of DAAs can hamper the protein translational process, several cellular mechanisms are dedicated to protecting the process against possible errors in protein synthesis and in its secondary structure. These mechanisms include two types of enzymes: D-amino acid oxidase (dehydrogenase in bacteria and plants) (Wang et al, 2012) and D-Tyr-tRNA deacylase (or D-aa-tRNA deacylase, DTD) (Bhatt et al, 2016;Hussain et al, 2006). Another mechanism is the ability of the ribosome's peptidyltransferase center to discriminate the chirality of amino acids (Englander et al, 2015).…”

Mechanistic insights into the slow peptide bond formation with D-amino acids in the ribosomal active site

“…Second, if D-aminoacyl-tRNAs are formed, they are typically deacylated by the D-aminoacyl-tRNA deacylase (DTD) (7,8). This enzyme is conserved across the three domains of life and prevents accumulation and toxicities of D-aminoacyl-tRNAs (9). Third, if a D-aminoacyl-tRNA escapes hydrolysis by DTD, it is recognized by the elongation factor EF-Tu.…”

Beyond the Wall: can D-Amino Acids and Small Molecule Inhibitors Eliminate Infections?

“…Unlike l -amino acids, DAAs are not used for ribosomal synthesis of proteins. Instead, their main role is as bacterial cell-wall constituents [5,6], though some exceptions have been observed [7]. Incorporation into PG is independent of DAA production; strains that fail to produce DAAs can nonetheless incorporate them into PG at the terminal position of the stem peptide.…”

“…Overall, those findings suggest an additional, unknown link between protein synthesis, cell-wall stress and the assembly of macrostructures. The specific role proposed for DTD in translational quality control of biofilm development makes this enzyme a compelling therapeutic target for biofilm infections [7].…”