Human isoleucyl-tRNA synthetase proteins, nucleic acids and test

Chemistry: molecular biology and microbiology – Enzyme – proenzyme; compositions thereof; process for...

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4352523, 43525411, 43525421, 4353201, 435325, 536 232, C12N 900, C12N 1500, C12N 114, C07H 2104

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057598339

ABSTRACT:
Isolated, recombinant nucleic acids which encode an isoleucyl-tRNA synthetase (IleRS) of human origin have been used to make expression constructs and transformed host cells for the production of a recombinant human IleRS. A recombinant enzyme has been purified, and is active in the specific aminoacylation of tRNA by isoleucine. Isolated, recombinant enzyme, and antibodies made specifically thereto, can be useful in assays to diagnose and monitor the autoimmune disease known as "antisynthetase syndrome." The essential isoleucyl-tRNA synthetases of microbes pathogenic in humans can be the targets of inhibitory agents having antimicrobial activity. A human isoleucyl-tRNA synthetase, isolated and purified, can be used to assess the toxic effect in humans of such an inhibitory agent in various biochemical activity assays. This human enzyme can also be expressed in "tester strains," whose cells rely upon the function of the human isoleucyl-tRNA synthetase for tRNA.sup.Ile charging. Such tester strains can be used to test for any toxic effects of an antimicrobial agent that specifically interacts with a heterologous human IleRS gene or gene product.

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