title: Post-transfer editing mechanism of a D-aminoacyl-tRNA deacylase-like domain in threonyl-tRNA synthetase from archaea.
abstract: To ensure a high fidelity during translation, threonyl-tRNA synthetases (ThrRSs) harbor an editing domain that removes noncognate L-serine attached to tRNAThr. Most archaeal ThrRSs possess a unique editing domain structurally similar to D-aminoacyl-tRNA deacylases (DTDs) found in eubacteria and eukaryotes that specifically removes D-amino acids attached to tRNA. Here, we provide mechanistic insights into the removal of noncognate L-serine from tRNAThr by a DTD-like editing module from Pyrococcus abyssi ThrRS (Pab-NTD). High-resolution crystal structures of Pab-NTD with pre- and post-transfer substrate analogs and with L-serine show mutually nonoverlapping binding sites for the seryl moiety. Although the pre-transfer editing is excluded, the analysis reveals the importance of main chain atoms in proper positioning of the post-transfer substrate for its hydrolysis. A single residue has been shown to play a pivotal role in the inversion of enantioselectivity both in Pab-NTD and DTD. The study identifies an enantioselectivity checkpoint that filters opposite chiral molecules and thus provides a fascinating example of how nature has subtly engineered this domain for the selection of chiral molecules during translation.
authors.affiliation: Centre for Cellular and Molecular Biology, Uppal Road, Hyderabad, India.
authors.forename: Tanweer
authors.initials: T
authors.lastname: Hussain
authors.forename: Shobha P
authors.initials: SP
authors.lastname: Kruparani
authors.forename: Biswajit
authors.initials: B
authors.lastname: Pal
authors.forename: Anne-Catherine
authors.initials: AC
authors.lastname: Dock-Bregeon
authors.forename: Shweta
authors.initials: S
authors.lastname: Dwivedi
authors.forename: Megala R
authors.initials: MR
authors.lastname: Shekar
authors.forename: Kotini
authors.initials: K
authors.lastname: Sureshbabu
authors.forename: Rajan
authors.initials: R
authors.lastname: Sankaranarayanan
mesh_terms: D000595:Amino Acid Sequence; D019843:Archaeal Proteins / Q000737:chemistry* / Q000235:genetics; D001665:Binding Sites; D008239:Lysine / Q000737:chemistry; D008958:Models, Molecular; D008969:Molecular Sequence Data; D017434:Protein Structure, Tertiary; D043903:Pyrococcus abyssi / Q000201:enzymology* / Q000235:genetics; D017393:RNA Editing; D012346:RNA, Transfer, Amino Acyl / Q000737:chemistry* / Q000235:genetics; D013237:Stereoisomerism; D013914:Threonine-tRNA Ligase / Q000737:chemistry* / Q000235:genetics; D046249:Transfer RNA Aminoacylation
chemical_list: D019843:Archaeal Proteins; D012346:RNA, Transfer, Amino Acyl; D013914:Threonine-tRNA Ligase; D008239:Lysine