3E33
Protein farnesyltransferase complexed with FPP and ethylenediamine scaffold inhibitor 7
Summary for 3E33
| Entry DOI | 10.2210/pdb3e33/pdb |
| Related | 1D8D 1KZO 1KZP 1SA4 1SA5 2IEJ 3E30 3E32 3E34 3E37 |
| Descriptor | Protein farnesyltransferase/geranylgeranyltransferase type-1 subunit alpha, Protein farnesyltransferase subunit beta, ZINC ION, ... (6 entities in total) |
| Functional Keywords | ftase, protein farnesyltransferase, farnesyltransferase, malaria, plasmodium, falciparum, antimalarial, inhibitor, ethylenediamine, prenyltransferase, transferase, metal-binding, phosphoprotein, zinc |
| Biological source | Rattus norvegicus (rat) More |
| Total number of polymer chains | 2 |
| Total formula weight | 93767.79 |
| Authors | Hast, M.A.,Beese, L.S. (deposition date: 2008-08-06, release date: 2009-03-10, Last modification date: 2024-02-21) |
| Primary citation | Hast, M.A.,Fletcher, S.,Cummings, C.G.,Pusateri, E.E.,Blaskovich, M.A.,Rivas, K.,Gelb, M.H.,Van Voorhis, W.C.,Sebti, S.M.,Hamilton, A.D.,Beese, L.S. Structural basis for binding and selectivity of antimalarial and anticancer ethylenediamine inhibitors to protein farnesyltransferase. Chem.Biol., 16:181-192, 2009 Cited by PubMed Abstract: Protein farnesyltransferase (FTase) catalyzes an essential posttranslational lipid modification of more than 60 proteins involved in intracellular signal transduction networks. FTase inhibitors have emerged as a significant target for development of anticancer therapeutics and, more recently, for the treatment of parasitic diseases caused by protozoan pathogens, including malaria (Plasmodium falciparum). We present the X-ray crystallographic structures of complexes of mammalian FTase with five inhibitors based on an ethylenediamine scaffold, two of which exhibit over 1000-fold selective inhibition of P. falciparum FTase. These structures reveal the dominant determinants in both the inhibitor and enzyme that control binding and selectivity. Comparison to a homology model constructed for the P. falciparum FTase suggests opportunities for further improving selectivity of a new generation of antimalarial inhibitors. PubMed: 19246009DOI: 10.1016/j.chembiol.2009.01.014 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.9 Å) |
Structure validation
Download full validation report
