| Autor: |
Taylor JS; Department of Biochemistry, Duke University Medical Center, Durham, NC 27710, USA., Reid TS, Terry KL, Casey PJ, Beese LS |
| Jazyk: |
angličtina |
| Zdroj: |
The EMBO journal [EMBO J] 2003 Nov 17; Vol. 22 (22), pp. 5963-74. |
| DOI: |
10.1093/emboj/cdg571 |
| Abstrakt: |
Protein geranylgeranyltransferase type-I (GGTase-I), one of two CaaX prenyltransferases, is an essential enzyme in eukaryotes. GGTase-I catalyzes C-terminal lipidation of >100 proteins, including many GTP- binding regulatory proteins. We present the first structural information for mammalian GGTase-I, including a series of substrate and product complexes that delineate the path of the chemical reaction. These structures reveal that all protein prenyltransferases share a common reaction mechanism and identify specific residues that play a dominant role in determining prenyl group specificity. This hypothesis was confirmed by converting farnesyltransferase (15-C prenyl substrate) into GGTase-I (20-C prenyl substrate) with a single point mutation. GGTase-I discriminates against farnesyl diphosphate (FPP) at the product turnover step through the inability of a 15-C FPP to displace the 20-C prenyl-peptide product. Understanding these key features of specificity is expected to contribute to optimization of anti-cancer and anti-parasite drugs. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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