Structures of Protein Farnesyltransferase

  • Stephen B. Long
  • Lorena S. Beese
Part of the Cancer Drug Discovery and Development book series (CDD&D)


High resolution three-dimensional crystal structures of protein farnesyltransferase (FTase) complexed with substrates and inhibitors provide a framework for understanding the molecular basis of substrate specificity and mechanism and may facilitate the development of improved chemotherapeutics. The 2.25Å resolution crystal structure of rat FTase provided the first structural information on any protein prenyltransferase enzyme (1). Rat FTase shares 93% sequence identity with the human enzyme and is predicted to be indistinguishable from human FTase in the active site region. Subsequently, a co-crystal structure of rat FTase with bound farnesyl diphosphate (FPP) revealed the location of the isoprenoid binding and gave insight into the molecular basis of isoprenoid substrate specificity (2). Recently, two co-crystal structures of rat FTase with a bound peptide substrate and a nonreactive isoprenoid diphosphate analog have identified the location of both the peptide and isoprenoid binding sites in a ternary enzyme complex (3,4). In this chapter we describe the recent crystal structures of rat FTase, and discuss their implications on understanding substrate specificity, mechanism, and inhibitor design.


Ternary Complex Peptide Substrate Hydrophobic Cavity Farnesyl Diphosphate Subunit Interface 
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Copyright information

© Springer Science+Business Media New York 2001

Authors and Affiliations

  • Stephen B. Long
  • Lorena S. Beese

There are no affiliations available

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