The phosphoprotein phosphatase family of Ser/Thr phosphatases as principal targets of naturally occurring toxins

• Tipo: Outra Publicação em Revista Científica Internacional
• Data: 2011

Autores

Susana R Pereira (Autor) Outra; Vitor M Vasconcelos (Autor) FCUP; Agostinho Antunes (Autor) FCUP

Revista

Título: Critical Reviews in Toxicology

Vol. 41

Páginas: 83-110

ISSN: 1040-8444

Editora: Taylor & Francis

Indexação

ISI Web of Knowledge - 49 Citações

Scopus - 53 Citações

Classificação Científica

FOS: Ciências médicas e da saúde > Medicina básica

Outras Informações

ID Authenticus: P-002-VJ4

DOI: 10.3109/10408444.2010.515564

Abstract (EN): Phosphoprotein phosphatases (PPPs) constitute one of three otherwise unrelated families of enzymes that specialize in removing the phosphate group from phosphorylated serine and threonine residues. The involvement of PPP enzymes in the regulation of processes such as gene expression, DNA replication, morphogenesis, synaptic transmission, glycogen metabolism, and apoptosis has underscored their potential as targets for the treatment of a variety of conditions such as cancer, diabetes, or Alzheimer''s disease. Interestingly, PPP enzymes also constitute the physiological target of multiple naturally occurring toxins, including microcystins from cyanobacteria and cantharidin from beetles. This review is devoted to the PPP family of enzymes--with a focus on the human PPPs--and the naturally occurring toxins that are known to potently impair their activity. The interaction of the toxins with the enzymes is evaluated in atomic detail to obtain insight on two complementary aspects: (1) which specific structural differences within the similarly folded catalytic core of the PPP enzymes explain their diverse sensitivities to toxin inhibition and (2) which structural features presented by the various toxins account for the differential inhibitory potency towards each PPP. These analyses take advantage of numerous site-directed mutagenesis studies, structure-activity evaluations, and recent crystallographic structures of PPPs bound to different toxins.</.

Idioma: Inglês

Tipo (Avaliação Docente): Científica

Nº de páginas: 28