Substrate specificity and nucleotides binding properties of NM23H2/nucleoside diphosphate kinase homolog from Plasmodium falciparum. 2010

Mahmoud Kandeel, and Yukio Kitade
Department of Pharmacology, Faculty of Veterinary Medicine, Kafr El-Shikh University, Kafr El-Shikh 33516, Egypt. mahmoud.kandeal@vet.kfs.edu.eg

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.

UI MeSH Term Description Entries
D009701 Nucleoside-Diphosphate Kinase An enzyme that is found in mitochondria and in the soluble cytoplasm of cells. It catalyzes reversible reactions of a nucleoside triphosphate, e.g., ATP, with a nucleoside diphosphate, e.g., UDP, to form ADP and UTP. Many nucleoside diphosphates can act as acceptor, while many ribo- and deoxyribonucleoside triphosphates can act as donor. EC 2.7.4.6. Deoxynucleoside Diphosphate Kinases,GDP Kinase,Nucleoside Diphosphokinases,Nucleoside-Diphosphate Kinases,Diphosphate Kinases, Deoxynucleoside,Diphosphokinases, Nucleoside,Kinase, GDP,Kinase, Nucleoside-Diphosphate,Kinases, Deoxynucleoside Diphosphate,Kinases, Nucleoside-Diphosphate,Nucleoside Diphosphate Kinase,Nucleoside Diphosphate Kinases
D009711 Nucleotides The monomeric units from which DNA or RNA polymers are constructed. They consist of a purine or pyrimidine base, a pentose sugar, and a phosphate group. (From King & Stansfield, A Dictionary of Genetics, 4th ed) Nucleotide
D010963 Plasmodium falciparum A species of protozoa that is the causal agent of falciparum malaria (MALARIA, FALCIPARUM). It is most prevalent in the tropics and subtropics. Plasmodium falciparums,falciparums, Plasmodium
D011485 Protein Binding The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments. Plasma Protein Binding Capacity,Binding, Protein
D011994 Recombinant Proteins Proteins prepared by recombinant DNA technology. Biosynthetic Protein,Biosynthetic Proteins,DNA Recombinant Proteins,Recombinant Protein,Proteins, Biosynthetic,Proteins, Recombinant DNA,DNA Proteins, Recombinant,Protein, Biosynthetic,Protein, Recombinant,Proteins, DNA Recombinant,Proteins, Recombinant,Recombinant DNA Proteins,Recombinant Proteins, DNA
D002151 Calorimetry The measurement of the quantity of heat involved in various processes, such as chemical reactions, changes of state, and formations of solutions, or in the determination of the heat capacities of substances. The fundamental unit of measurement is the joule or the calorie (4.184 joules). (McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed)
D004734 Energy Metabolism The chemical reactions involved in the production and utilization of various forms of energy in cells. Bioenergetics,Energy Expenditure,Bioenergetic,Energy Expenditures,Energy Metabolisms,Expenditure, Energy,Expenditures, Energy,Metabolism, Energy,Metabolisms, Energy
D013379 Substrate Specificity A characteristic feature of enzyme activity in relation to the kind of substrate on which the enzyme or catalytic molecule reacts. Specificities, Substrate,Specificity, Substrate,Substrate Specificities
D015153 Blotting, Western Identification of proteins or peptides that have been electrophoretically separated by blot transferring from the electrophoresis gel to strips of nitrocellulose paper, followed by labeling with antibody probes. Immunoblotting, Western,Western Blotting,Western Immunoblotting,Blot, Western,Immunoblot, Western,Western Blot,Western Immunoblot,Blots, Western,Blottings, Western,Immunoblots, Western,Immunoblottings, Western,Western Blots,Western Blottings,Western Immunoblots,Western Immunoblottings

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