Editing of Homocysteine by Aminoacyl-tRNA Synthetases

  • Jakubowski, Hieronim (PI)

Project Details

Description

0089984

Jakubowski

Living organisms possess error-correcting mechanisms which assure accurate synthesis of their proteins according to the genetic information contained in DNA. One such mechanism involves editing of the non-protein amino acid homocysteine . Homocysteine, an obligatory precursor of the protein amino acid methionine, is misactivated in the cell by some tRNA synthetases at a high frequency. Incorporation of homocysteine into cellular protein is prevented by an error-correcting mechanism of the synthetases which convert misactivated homocysteine into a thiolactone. Different cellular pools of homocysteine are not equally accessible to each synthetase, suggesting compartmentalization of homocysteine metabolism. The present project will determine the physical/biochemical basis for compartmentalization of homocysteine editing in the bacterium Escherichia coli. A role for the carboxy-terminal region of methionyl-tRNA synthetase in editing will be examined and component(s) of the methionine biosynthetic pathway which interact with methionyl-tRNA synthetase will be identified using biochemical and genetic approaches. Studies of molecular details of homocysteine editing are important. This project will elucidate a major aspect of the extraordinary accuracy in the flow of genetic information, i.e., the molecular basis of metabolite channeling in an amino acid biosynthetic pathway that limits the need for editing by tRNA synthetases

StatusFinished
Effective start/end date5/1/0112/31/04

Funding

  • National Science Foundation: $330,000.00

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