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

• Type: Another Publication in an International Scientific Journal
• Date: 2011

Authors

Susana R Pereira (Author) Other; Vitor M Vasconcelos (Author) FCUP; Agostinho Antunes (Author) FCUP

Journal

Title: Critical Reviews in Toxicology

Vol. 41

Pages: 83-110

ISSN: 1040-8444

Publisher: Taylor & Francis

Indexing

ISI Web of Knowledge - 49 Citations

Scopus - 53 Citations

Scientific classification

FOS: Medical and Health sciences > Basic medicine

Other information

Authenticus ID: 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.</.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 28