Chirality Check

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Science  10 Jan 2014:
Vol. 343, Issue 6167, pp. 119
DOI: 10.1126/science.343.6167.119-b

Most biological macromolecules are homochiral, and enzymes help to maintain this state of affairs; for example, checkpoints ensure that only l-amino acids are incorporated into proteins during translation. Among these enzymes is d-aminoacyl-tRNA deacylase (DTD), which removes d-amino acids mischarged onto tRNAs. Three types of DTDs have been identified, with the most common form being present in many bacteria and all eukaryotes. DTD faces the mechanistic challenge of acting on diverse d-aminoacyl-tRNAs (d-aa-tRNAs) while not harming l-aminoacyl-tRNAs (l-aa-tRNAs) that are present at much higher concentrations. Although crystal structures have been determined for DTD in the apo form and bound to free d-amino acids, the structural basis of enantioselectivity remained unclear. Ahmad et al. report the crystal structure of dimeric DTD from Plasmodium falciparum in complex with a substrate analog that mimics d-tyrosine attached to the 3′-OH of the terminal adenosine of tRNA. A critical role in shaping the active site for enantioselectivity is played by a Gly-cisPro motif that is inserted from one DTD monomer into the active site of the other monomer. Mainly main-chain atoms from DTD interact with the substrate, facilitating interaction with a range of d-aa-tRNAs. On the basis of mutational studies of active site residues, the authors suggest an RNA-assisted catalytic mechanism in which the RNA 2′-OH activates a water molecule.

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