4O7I

Structural and functional characterization of 3'(2'),5'-bisphosphate nucleotidase1 from Entamoeba histolytica

Replaces:  4GDG

Summary for 4O7I

• Entry DOI: 10.2210/pdb4o7i/pdb
• Descriptor: 3'(2'),5'-bisphosphate nucleotidase, putative, MAGNESIUM ION, PHOSPHATE ION, ... (4 entities in total)
• Functional Keywords: li sensitive/mg dependent phosphatase, dephosphorylation, hydrolase
• Biological source: Entamoeba histolytica
• Total number of polymer chains: 1
• Total formula weight: 36273.30

Authors

Tarique, K.F.,Rehman, S.A.A.,Gourinath, S. (deposition date: 2013-12-24, release date: 2014-01-22, Last modification date: 2023-11-08)

Primary citation

Faisal Tarique, K.,Arif Abdul Rehman, S.,Gourinath, S.
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
Acta Crystallogr.,Sect.D, 70:2019-2031, 2014

PubMed Abstract: 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 Å resolution, respectively. The PAP phosphatase-1 structure is divided into two domains, namely α+β and α/β, 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.

PubMed: 25004978
DOI: 10.1107/S1399004714010268

Experimental method

X-RAY DIFFRACTION (2.11 Å)