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Publication Abstract from PubMed

The enzyme 3'-phosphoadenosine 5'-phosphatase-1 (PAP phosphatase-1) is a member of the Li(+)-sensitive Mg(2+)-dependent phosphatase superfamily, or inositol monophosphatase (IMPase) superfamily, and is an important regulator of the sulfate-activation pathway in all living organisms. Inhibition of this enzyme leads to accumulation of the toxic byproduct 3'-phosphoadenosine 5'-phosphate (PAP), which could be lethal to the organism. Genomic analysis of Entamoeba histolytica suggests the presence of two isoforms of PAP phosphatase. The PAP phosphatase-1 isoform of this organism is shown to be active over wide ranges of pH and temperature. Interestingly, this enzyme is inhibited by submillimolar concentrations of Li(+), while being insensitive to Na(+). Interestingly, the enzyme showed activity towards both PAP and inositol 1,4-bisphosphate and behaved as an inositol polyphosphate 1-phosphatase. Crystal structures of this enzyme in its native form and in complex with adenosine 5'-monophosphate have been determined to 2.1 and 2.6 A resolution, respectively. The PAP phosphatase-1 structure is divided into two domains, namely alpha+beta and alpha/beta, and the substrate and metal ions bind between them. This is a first structure of any PAP phosphatase to be determined from a human parasitic protozoan. This enzyme appears to function using a mechanism involving three-metal-ion assisted catalysis. Comparison with other structures indicates that the sensitivity to alkali-metal ions may depend on the orientation of a specific catalytic loop.

Structural elucidation of a dual-activity PAP phosphatase-1 from Entamoeba histolytica capable of hydrolysing both 3'-phosphoadenosine 5'-phosphate and inositol 1,4-bisphosphate.,Faisal Tarique K, Arif Abdul Rehman S, Gourinath S Acta Crystallogr D Biol Crystallogr. 2014 Jul 1;70(Pt 7):2019-31. doi:, 10.1107/S1399004714010268. Epub 2014 Jun 29. PMID:25004978^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.