Inhibitors of protein: geranylgeranyl transferases.
Curr Med Chem
; 13(20): 2385-427, 2006.
Article
em En
| MEDLINE
| ID: mdl-16918362
ABSTRACT
The enzyme proteingeranylgeranyl 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 proteingeranylgeranyl 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, proteingeranylgeranyl transferase-2 (PGGT-2), are also included.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Alquil e Aril Transferases
/
Inibidores Enzimáticos
Limite:
Animals
/
Humans
Idioma:
En
Ano de publicação:
2006
Tipo de documento:
Article