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- W809497570 abstract "The synthesis of deoxyribonucleoside triphosphates (dNTPs), building blocks of DNA, can be achieved by two different pathways in the cell. One is called de novo synthesis and the other is known as salvage pathway. The de novo pathway involves synthesis of dNTPs by utilizing basic molecules like sugars, amino acids, CO2, NH3, etc., while in the other pathway, dNTPs are formed by salvaging intra- or extra-cellular deoxyribonucleosides (dNs). Deoxyribonucleoside kinases (dNKs) catalyze the rate-limiting step of the nucleoside salvage pathway by converting the dNs into the corresponding deoxyribonucleoside monophosphates and play an important role in maintaining the balanced dNTP pools in the cell. Furthermore, dNKs show a great deal of multiplicity among different organisms and present an excellent choice to study different evolutionary phenomena, such as, the origin of regulatory activities and gene/enzyme duplication.The present study deals with the characterization of different dNKs in order to understand their structure-function relationship, substrate specificities and evolutionary history. The ‘ATP-induced’ dimer/tetramer shift on thymidine kinase 1 (TK1) from different organisms was studied to comprehend the evolutionary origin of oligomerization based regulation of TK1. The results suggested that the dimer form is the original form and the tetramer form has originated in early animals to serve as a fine-tuning mechanism for the regulation of TK1 activity.In addition, the evolutionary background of various dNKs was studied. An apparent duplication of deoxycytidine kinase (dCK) in some vertebrates and loss of deoxyguanosine kinase (dGK) in one of the bird families were observed. The kinetic properties of the recombinant dCK/dGK-like enzymes from an amphibian, Xenopus laevis, and a bird, Gallus gallus, were determined and the sub-cellular localization of these enzymes was predicted. It seems that substrate specificity and sub-cellular localization are the likely biological forces behind vertebrate dCK/dGK evolution.Finally, the dNK activities in sub-cellular fractions of plants, Arabidopsis thaliana and Solanum tuberosum, were analyzed and the results showed that most of the plant dNK activity mainly occurs in mitochondria, but not in chloroplasts." @default.
- W809497570 created "2016-06-24" @default.
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- W809497570 date "2013-01-01" @default.
- W809497570 modified "2023-09-25" @default.
- W809497570 title "The Structure-Function Relationship and Evolution of Deoxyribonucleoside Kinases" @default.
- W809497570 hasPublicationYear "2013" @default.
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