The Search for the Mechanism of the Reaction Catalyzed by Farnesyltransferase

• Tipo: Artigo em Revista Científica Internacional
• Data: 2009

Autores

Sergio Filipe Sousa (Autor) FCUP; Pedro Alexandrino Fernandes (Autor) FCUP; Maria Joao Ramos (Autor) FCUP

Revista

Título: Chemistry - A European Journal

Vol. 15

Páginas: 4243-4247

ISSN: 0947-6539

Editora: Wiley-Blackwell

Indexação

ISI Web of Knowledge - 26 Citações

Scopus - 28 Citações

Classificação Científica

FOS: Ciências exactas e naturais > Química

Outras Informações

ID Authenticus: P-003-PCW

DOI: 10.1002/chem.200802745

Abstract (EN): An experimental study was conducted to fully characterize the mechanism of the reaction catalyzed by FTase (farnesyltransferase) by determining the first real quantum chemistry transition-state structure for the concerted reaction catalyzed this enzyme. This was done using a 72-atom quantum-mechanical active-site model that includes the full zinc coordination sphere, an ethane thiolate to represent the CAAX cysteine residue, the pyrophosphate moiety, and the first isoprenoid subunit of FPP (farnesyldiphosphate). Special care was taken to accurately account for the effect of the enzyme, by including all the main specific interactions between the enzyme, the two model substrate and the metal coordination sphere. The results indicate a FPP(C1)-S(CAAX) distance of 2.955 Å and a C1-O(FPP) bond length of 1.779 Å for the transition state structure. A comparison of the values for the reactants and transition state show that the charge at the FPP C1 and C2 increases from the reactants to the transition state, whereas negative charges form on zinc bound sulfur atom and pyrophosphate oxygen atoms.

Idioma: Inglês

Tipo (Avaliação Docente): Científica

Nº de páginas: 5