Minor groove recognition of the critical acceptor helix base pair by an appended module of a class II tRNA synthetase.

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Buechter DD, Schimmel P

Minor groove recognition of the critical acceptor helix base pair by an appended module of a class II tRNA synthetase.

Biochemistry. 1995 May 9;34(18):6014-9.

PubMed ID

7742303 [ View in PubMed

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Abstract

The class-defining active site domain of the 10 class II tRNA synthetases is well conserved and, based on the crystal structure of aspartyl-tRNA synthetase, approaches the end of the tRNA acceptor stem from the major groove side of the helix. Paradoxically, for the class II alanyl-tRNA synthetase (AlaRS), aminoacylation is dependent on minor groove recognition of an acceptor helix G3.U70 base pair. Additional contributions to aminoacylation efficiency are made by the A73 "discriminator" base and G2.C71 base pair located at the end of the acceptor stem. Using microhelix substrates containing only the first four base pairs of the alanine tRNA acceptor helix, we demonstrated that the catalytic center of AlaRS with the three class-defining sequence motifs contains determinants for recognition of A73 and G2.C71. However, this structural unit does not discriminate between different base pairs at the critical 3.70 position. Discrimination at G3.U70 was mapped to a 76 amino acid polypeptide outside the catalytic center. We propose that the G3.U70 recognition motif is a structural appendage that folds back to the catalytic center to make contact with the bound acceptor stem. A "fold-back" appendage provides a specific mechanism for minor groove recognition of the acceptor helix by a class II tRNA synthetase.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Alanine	Alanine--tRNA ligase, cytoplasmic	Protein	Humans	Unknown	Not Available	Details
Alanine	Alanine--tRNA ligase, mitochondrial	Protein	Humans	Unknown	Not Available	Details