Substrate specificity and nucleotides binding properties of NM23H2/nucleoside diphosphate kinase homolog from Plasmodium falciparum.
Nucleoside diphosphate kinases (NDKs) play a key role in maintaining the intracellular energy resources as well as the balance of nucleotide pools. Recently, attention has been directed to NDKs owing to its role in activating various chemotherapeutic agents. The binding affinity of different nucleotides with P. falciparum NDK was varied according to the following order ADP ~ GDP > dGDP > dADP > dTDP > CDP > dCDP > UDP. The binding of purines nucleotides was stronger than pyrimidines. Furthermore, PfNDK showed more preferences to ribonucleotides over deoxyribonucleotides. Pyrimidines showed lower negative free energy compared with that of purines. The interaction of all nucleotides showed favorable enthalpic and entropic terms. However, the enthalpic terms were the main deriving forces for purine nucleotides, while the entropic contributions were the predominant forces for pyrimidines. Interestingly, TDP showed marked affinity and more favorable enthalpic and less entropic contributions. In conclusion, the size of nucleotide was the critical factor in PfNDK ligand affinity.
Kandeel
Mahmoud
M
Department of Pharmacology, Faculty of Veterinary Medicine, Kafr El-Shikh University, Kafr El-Shikh 33516, Egypt. mahmoud.kandeal@vet.kfs.edu.eg
Kitade
Yukio
Y
D015153:Blotting, Western; D002151:Calorimetry; D004734:Energy Metabolism; D009701:Nucleoside-Diphosphate Kinase / Q000378:metabolism*; D009711:Nucleotides / Q000378:metabolism*; D010963:Plasmodium falciparum / Q000201:enzymology*; D011485:Protein Binding; D011994:Recombinant Proteins / Q000378:metabolism*; D013379:Substrate Specificity
D009711:Nucleotides; D011994:Recombinant Proteins; D009701:Nucleoside-Diphosphate Kinase