1KZP
PROTEIN FARNESYLTRANSFERASE COMPLEXED WITH A FARNESYLATED K-RAS4B PEPTIDE PRODUCT
Summary for 1KZP
| Entry DOI | 10.2210/pdb1kzp/pdb |
| Related | 1D8D 1FT1 1FT2 1JCQ 1kzo 1kzr |
| Descriptor | Protein Farnesyltransferase alpha subunit, Protein Farnesyltransferase beta subunit, Farnesylated K-Ras4B peptide product, ... (7 entities in total) |
| Functional Keywords | ftase, pft, pftase, ft, fpt, farnesyltransferase, farnesyl transferase, farnesyl protein transferase, caax, ras cancer, transferase-transferase substrate complex, transferase/transferase substrate |
| Biological source | Rattus norvegicus (Norway rat) More |
| Total number of polymer chains | 3 |
| Total formula weight | 94511.03 |
| Authors | Long, S.B.,Casey, P.J.,Beese, L.S. (deposition date: 2002-02-07, release date: 2002-10-16, Last modification date: 2023-08-16) |
| Primary citation | Long, S.B.,Casey, P.J.,Beese, L.S. Reaction path of protein farnesyltransferase at atomic resolution Nature, 419:645-650, 2002 Cited by PubMed Abstract: Protein farnesyltransferase (FTase) catalyses the attachment of a farnesyl lipid group to numerous essential signal transduction proteins, including members of the Ras superfamily. The farnesylation of Ras oncoproteins, which are associated with 30% of human cancers, is essential for their transforming activity. FTase inhibitors are currently in clinical trials for the treatment of cancer. Here we present a complete series of structures representing the major steps along the reaction coordinate of this enzyme. From these observations can be deduced the determinants of substrate specificity and an unusual mechanism in which product release requires binding of substrate, analogous to classically processive enzymes. A structural model for the transition state consistent with previous mechanistic studies was also constructed. The processive nature of the reaction suggests the structural basis for the successive addition of two prenyl groups to Rab proteins by the homologous enzyme geranylgeranyltransferase type-II. Finally, known FTase inhibitors seem to differ in their mechanism of inhibiting the enzyme. PubMed: 12374986DOI: 10.1038/nature00986 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.1 Å) |
Structure validation
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