Crystal structure of protein farnesyltransferase at 2.25 angstrom resolution.
Published
Journal Article
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.
Full Text
Duke Authors
Cited Authors
- Park, HW; Boduluri, SR; Moomaw, JF; Casey, PJ; Beese, LS
Published Date
- March 21, 1997
Published In
Volume / Issue
- 275 / 5307
Start / End Page
- 1800 - 1804
PubMed ID
- 9065406
Pubmed Central ID
- 9065406
International Standard Serial Number (ISSN)
- 0036-8075
Digital Object Identifier (DOI)
- 10.1126/science.275.5307.1800
Language
- eng
Conference Location
- United States