Inhibition of farnesyltransferase: A rational approach to treat cancer?

Figures & data

Figure 1 Post translational modification of Ras.

Table I.  Various FTase structures deposited in databank with their PDB codes, resolution and active site amino acid residues.

Pdb Code	Resolution (A^o)	Active site residues
1LD7	2.00	His 862, Tyr 800, Asp 797, Asp 794, Arg 791, His 748, Lys 164
1LD8	1.80	His 862, Tyr 800, Cys 799, Asp 797, Lys 794, Arg 791, His 748, His 201, Lys 164, Gln 167
1MZC	2.00	His 862, Tyr 800, Asp 797, Lys 794, Arg 791, His 748, Tyr 166, Lys 164
1N9A	3.20	Asp 359, Arg 291, His 248, Lys 164
1NI1	2.30	Tyr 300, Arg 291, His 248, Lys 164, Tyr 93
1S63	1.90	His 362, Tyr 300, Asp 297, Lys 294, Arg 291, His 248, Lys 164
1SA4	2.10	Tyr 300, Arg 291, His 248, Lys 164
1O5M	2.30	Try 300, Arg 291, His 248, Lys 164
1NL4	2.70	His 362, Tyr 300, Asp 297, His 248, Lys 164, Tyr 166
1X81	3.50	No ligand
1FT1	2.25	No ligand

Residues marked bold form hydrogen bond with the ligand.

Figure 2 Farnesyltransferase enzyme complexed with farnesyldiphosphate (PDB code: 1FPP).

Figure 3 Farnesyltransferase enzyme complexed with tipifarnib (PDB code: 1SA4).

Figure 4 STDDEV*COEFF contour plots for 3-aminopyrrolidinones. (A) CoMFA steric (B) CoMFA electrostatic (C) CoMSIA hydrophobic maps superimposed on FTase active site.