Molecular dynamics studies of a hexameric purine nucleoside phosphorylase.
Purine nucleoside phosphorylase (PNP) (EC.2.4.2.1) is an enzyme that catalyzes the cleavage of N-ribosidic bonds of the purine ribonucleosides and 2-deoxyribonucleosides in the presence of inorganic orthophosphate as a second substrate. This enzyme is involved in purine-salvage pathway and has been proposed as a promising target for design and development of antimalarial and antibacterial drugs. Recent elucidation of the three-dimensional structure of PNP by X-ray protein crystallography left open the possibility of structure-based virtual screening initiatives in combination with molecular dynamics simulations focused on identification of potential new antimalarial drugs. Most of the previously published molecular dynamics simulations of PNP were carried out on human PNP, a trimeric PNP. The present article describes for the first time molecular dynamics simulations of hexameric PNP from Plasmodium falciparum (PfPNP). Two systems were simulated in the present work, PfPNP in ligand free form, and in complex with immucillin and sulfate. Based on the dynamical behavior of both systems the main results related to structural stability and protein-drug interactions are discussed.
Zanchi
Fernando Berton
FB
Universidade Federal de Rondônia, Porto Velho, RO, Brazil.
Caceres
Rafael Andrade
RA
Stabeli
Rodrigo Guerino
RG
de Azevedo
Walter Filgueira
WF
D001665:Binding Sites; D055162:Biocatalysis; D004795:Enzyme Stability; D056004:Molecular Dynamics Simulation; D010710:Phosphates / Q000378:metabolism; D010963:Plasmodium falciparum / Q000201:enzymology*; D018583:Pliability; D055503:Protein Multimerization; D017434:Protein Structure, Tertiary; D011684:Purine Nucleosides / Q000737:chemistry / Q000378:metabolism; D011683:Purine-Nucleoside Phosphorylase / Q000737:chemistry* / Q000378:metabolism; D011744:Pyrimidinones / Q000737:chemistry / Q000378:metabolism; D013431:Sulfates / Q000378:metabolism; D013997:Time Factors
D010710:Phosphates; D011684:Purine Nucleosides; D011744:Pyrimidinones; D013431:Sulfates; C113101:forodesine; D011683:Purine-Nucleoside Phosphorylase