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Inhibitors of protein: geranylgeranyl transferases.

Authors :
El Oualid F
Cohen LH
van der Marel GA
Overhand M
Source :
Current medicinal chemistry [Curr Med Chem] 2006; Vol. 13 (20), pp. 2385-427.
Publication Year :
2006

Abstract

The enzyme protein:geranylgeranyl transferase-1 (PGGT-1 or GGTase-I) catalyzes the geranylgeranylation of cysteine residues near the C-termini of a variety of proteins, including most monomeric GTP binding precursor proteins belonging to the Rho, Rac and Rap subfamilies. These proteins are involved in signaling pathways controlling important processes such as cell differentiation and growth. In the framework of the development of therapeutics against disorders associated with aberrant cell proliferation, the interference with these signal transduction cascades has been a major focus of investigation. For instance inhibitors of PGGT-1 have shown promise in the treatment of cancer, smooth muscle hyperplasia as well as parasitic infections, such as malaria. In this review, structural and mechanistic aspects of the protein:geranylgeranyl transferases are discussed as well as their importance with respect to the terpene metabolism. An extensive summary of reported inhibitors of PGGT-1, classified as natural products, peptide substrate (Ca(1)a(2)L box), terpene substrate (geranylgeranyl pyrophosphate) and others, is presented. The few known inhibitors of the other geranylgeranylating enzyme, protein:geranylgeranyl transferase-2 (PGGT-2), are also included.

Details

Language :
English
ISSN :
0929-8673
Volume :
13
Issue :
20
Database :
MEDLINE
Journal :
Current medicinal chemistry
Publication Type :
Academic Journal
Accession number :
16918362
Full Text :
https://doi.org/10.2174/092986706777935078