1FT1

CRYSTAL STRUCTURE OF PROTEIN FARNESYLTRANSFERASE AT 2.25 ANGSTROMS RESOLUTION

Summary for 1FT1

• Entry DOI: 10.2210/pdb1ft1/pdb
• Descriptor: PROTEIN FARNESYLTRANSFERASE, ZINC ION, ... (4 entities in total)
• Functional Keywords: cancer therapeutics, g proteins, prenyltransferase, signal transduction, ras, transferase
• Biological source: Rattus norvegicus (Norway rat); More
• Total number of polymer chains: 2
• Total formula weight: 92885.84

Authors

Beese, L.S.,Park, H.-W. (deposition date: 1997-03-17, release date: 1998-03-18, Last modification date: 2024-02-07)

Primary citation

Park, H.W.,Boduluri, S.R.,Moomaw, J.F.,Casey, P.J.,Beese, L.S.
Crystal structure of protein farnesyltransferase at 2.25 angstrom resolution.
Science, 275:1800-1804, 1997

PubMed Abstract: Protein farnesyltransferase (FTase) catalyzes the carboxyl-terminal lipidation of Ras and several other cellular signal transduction proteins. The essential nature of this modification for proper function of these proteins has led to the emergence of FTase as a target for the development of new anticancer therapy. Inhibition of this enzyme suppresses the transformed phenotype in cultured cells and causes tumor regression in animal models. The crystal structure of heterodimeric mammalian FTase was determined at 2.25 angstrom resolution. The structure shows a combination of two unusual domains: a crescent-shaped seven-helical hairpin domain and an alpha-alpha barrel domain. The active site is formed by two clefts that intersect at a bound zinc ion. One cleft contains a nine-residue peptide that may mimic the binding of the Ras substrate; the other cleft is lined with highly conserved aromatic residues appropriate for binding the farnesyl isoprenoid with required specificity.

PubMed: 9065406
DOI: 10.1126/science.275.5307.1800

Experimental method

X-RAY DIFFRACTION (2.25 Å)