Disease relevance of metG

• We have analyzed, by site-directed mutagenesis, the molecular basis of the editing function and its relation to the synthetic function of Escherichia coli methionyl-tRNA synthetase [1].

High impact information on metG

• Screening of a saturation mutagenesis library of the E. coli methionyl-tRNA synthetase (MetRS) led to the discovery of three MetRS mutants capable of incorporating the long-chain amino acid azidonorleucine into recombinant proteins with modest efficiency [2].
• The model also explains why the noncognate homocysteine is edited by methionyl-tRNA synthetase [1].
• Consistent with these functions, side chains of Trp-305 and Tyr-15 are localized on opposite sides of the cavity forming a putative methionine binding pocket that is observed in the three-dimensional crystallographic structure of methionyl-tRNA synthetase [1].
• Identification of the metal ligands and characterization of a putative zinc finger in methionyl-tRNA synthetase [3].
• Taken together, our studies identify the 4 cysteine residues in the zinc finger-like domain as the metal binding ligands in the E. coli methionyl-tRNA synthetase [3].

Chemical compound and disease context of metG

• Activation of methionine by Escherichia coli methionyl-tRNA synthetase [4].
• In E. coli, most of the energy cost of proofreading by methionyl-tRNA synthetase is due to editing of the incorrect product, homocysteinyl adenylate [5].

Biological context of metG

• A truncated form of the methionyl-tRNA synthetase (delta MTS), which has been cloned, overproduced, and characterized, was used in an attempt to better understand the role of the enzyme-bound zinc in the amino-acylation process [3].
• The active site of methionyl-tRNA synthetase (MetRS) possesses two functions: synthetic, which provides Met-tRNA for protein synthesis, and editing, which rejects inadvertently misactivated homocysteine [6].
• Escherichia coli methionyl-tRNA synthetase consists of catalytic, anticodon-binding, and dimerization domains [7].

Analytical, diagnostic and therapeutic context of metG

• Studies of an error-editing function of bacterial methionyl-tRNA synthetase have led to the discovery of a distinct chemical mechanism of editing and to molecular dissection of the dual synthetic-editing function of the active site of the synthetase [5].

References