On the Stereochemical Course of Human Protein-Farnesyl Transferase
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- 作者：YongQi Mu ; Charles A. Omer ; and Richard A. Gibbs
- 刊名：Journal of the American Chemical Society
- 出版年：1996
- 出版时间：February 28, 1996
- 年：1996
- 卷：118
- 期：8
- 页码：1817 - 1823
- 全文大小：487K
- 年卷期：v.118,no.8(February 28, 1996)
- ISSN：1520-5126
文摘
The enzyme protein-farnesyl transferase (PFTase) catalyzes thefarnesylation of the Ras protein and certainother proteins, using farnesyl diphosphate (FPP) as the prenyl source.Because of the important role of mutant Rasproteins in cancer, inhibitors of PFTase are of great interest aspotential novel anticancer agents. The design of suchagents would be aided by a greater knowledge of the mechanism ofPFTase. We have determined the stereochemicalcourse of PFTase using the two stereospecifically prepared isomers of[1-2H]-FPP as substrates in conjunction with1H-NMR analysis of the farnesylated peptide products.This confirms that PFTase carries out the transfer ofthefarnesyl group with inversion of configuration. Combined with theresults of studies on fluorinated analogs of FPPas PFTase substrates (Dolence, J. M.; Poulter, C. D. Proc.Natl. Acad. Sci.U.S.A. 1995, 92,5008), this indicates thatthe mechanistic course of PFTase is similar to that of the prototypicalprenyltransferase enzyme, FPP synthase.