purine nucleoside phosphorylase

A resistant mutant of Plasmodium falciparum purine nucleoside phosphorylase uses wild-type neighbors to maintain parasite survival

Tags:

resistant mutant, plasmodium falciparum, purine nucleoside phosphorylase, malaria

Author(s):

Minnow YVT, Harijan RK, Schramm VL

Reference:

J Biol Chem. 2021 Jan 29:100342

Plasmodium falciparum purine nucleoside phosphorylase (PfPNP) catalyzes an essential step in purine salvage for parasite growth. 4'-Deaza-1'- Aza-2'-Deoxy-1'-(9-Methylene)-Immucillin-G (DADMe- ImmG) is a transition state analog inhibitor of this enzyme, and P. falciparum infections in an Aotus primate malaria model can be cleared by oral administration of DADMe-ImmG. P. falciparum cultured under increasing DADMe-ImmG drug pressure exhibited PfPNP gene amplification, increased protein expression and point mutations involved in DADMe-ImmG binding.

NOT Open Access | Plasmodium falciparum purine nucleoside phosphorylase as a model in the search for new inhibitors by high throughput screening

Tags:

plasmodium falciparum, purine nucleoside phosphorylase, in vitro, in vivo

Author(s):

Holanda RJ, Deves C, Pereira da Silva LH, et al.

Reference:

Int J Biol Macromol. 2020 Dec 15;165(Pt B):1832-1841

Studies have shown that inhibition of Plasmodium falciparum Purine Nucleoside Phosphorylase (PfPNP) blocks the purine salvage pathway in vitro and in vivo. In this study, PfPNP was evaluated as a model in the search for new inhibitors using surface plasmon resonance (SPR). Its expression, purification, oligomeric state, kinetic constants, calorimetric parameters and kinetic mechanisms were obtained. PfPNP was immobilized on a CM5 sensor chip and sensorgrams were produced through binding the enzyme to the substrate MESG and interactions between molecules contained in 10 fractions of natural extracts.

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purine nucleoside phosphorylase