Figure 3.

The co-crystal structure of the C. neoformans FTase with tipifarnib suggests that inhibitor derivatization may lead to increased affinity and fungal selectivity. A, chemical structure of tipifarnib. B, surface representation of the structure of C. neoformans FTase in complex with farnesyl pyrophosphate analog, FPT-II, and tipifarnib (PDB entry 3SFX). The ligands are represented as sticks and color-coded according to heteroatom composition. Tipifarnib coordinates with the catalytic Zn²⁺ ion (pink) and could be derivatized to increase interactions with the product exit groove (arrow) and peptide-binding site (asterisk).