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1 Mechanism of catalysis by protein farnesyltransferase

Elsevier Inc.
DOI: 10.1016/s1874-6047(01)80014-7
  • Biology
  • Chemistry
  • Design


Publisher Summary This chapter discusses the mechanism of catalysis with particular focus on the enzymology of addition of the farnesyl isoprenoid to cellular proteins. Efforts to design selective cell-active inhibitors of the enzyme for evaluation as anticancer agents have been successful; the acquisition of mechanistic and structural information on protein farnesyltransferase (FTase) has greatly aided these drug discovery programs. Remaining questions on this enzyme are primarily centered on the definition of the precise chemical mechanism of the reaction and the structural basis for the ability of the enzyme to discriminate among similar protein substrates. While the close similarities in both structure and function of FTase and geranylgeranyltransferase type I (GGTase-I) make it likely that both enzymes use a similar catalytic mechanism, it will still be important to conduct detailed studies with GGTase-I to determine whether there are important differences among these enzymes.

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