Pedro Manuel Azevedo Alexandrino Fernandes

Publicações :: Ver detalhe

Artigo em Revista

Publicação FCT	Artigo publicado em revista internacional
Autor(es)	Sérgio F. Sousa; Pedro Alexandrino Fernandes; Maria J. Ramos;
Título	Effective Tailor-Made Force Field Parameterization of the Several Zn Coordination Environments in the Puzzling FTase Enzyme: Opening the Door to the Full Understanding of its Elusive Catalytic Mechanism
Jornal	Theoretical Chemistry Accounts
Volume	117
Número
Páginas	171-181
Mês
Ano	2007
Nota
Chave para citação
Resumo	Protein farnesyltransferase (FTase) is very promising anticancer drug target, with several drugs in advanced stages of clinical testing. However, in spite of the thrilling achievements in the development of farnesyltransferase inhibitors (FTIs) over the past few years, the farnesylation mechanism remains, to some degree, a mystery. This work reports the determination and validation of three sets of molecular mechanical parameters specifically tailored to accurately account for the very specific nature of the several Zn coordination spheres formed during the unclear catalytic pathway of this puzzling metalloenzyme, and built on the top of recent experimental and theoretical results that have dramatically changed the way how the farnesylation mechanism is perceived. Extensive validation studies with 14 FTase crystallographic structures, EXAFS data, DFT, and QM/MM theoretical calculations are presented.
Ficheiro	- Não definido.
URL
BibTeX	@ARTICLE { AUTHOR="Sérgio F. Sousa and Pedro Alexandrino Fernandes and Maria J. Ramos", TITLE="Effective Tailor-Made Force Field Parameterization of the Several Zn Coordination Environments in the Puzzling FTase Enzyme: Opening the Door to the Full Understanding of its Elusive Catalytic Mechanism", JOURNAL="Theoretical Chemistry Accounts", VOLUME="117", NUMBER="", PAGES="171-181", MONTH="", YEAR="2007", NOTE="", CITEKEY="", ABSTRACT="Protein farnesyltransferase (FTase) is very promising anticancer drug target, with several drugs in advanced stages of clinical testing. However, in spite of the thrilling achievements in the development of farnesyltransferase inhibitors (FTIs) over the past few years, the farnesylation mechanism remains, to some degree, a mystery. This work reports the determination and validation of three sets of molecular mechanical parameters specifically tailored to accurately account for the very specific nature of the several Zn coordination spheres formed during the unclear catalytic pathway of this puzzling metalloenzyme, and built on the top of recent experimental and theoretical results that have dramatically changed the way how the farnesylation mechanism is perceived. Extensive validation studies with 14 FTase crystallographic structures, EXAFS data, DFT, and QM/MM theoretical calculations are presented. ", URL="" }

FCUP 2014