Department of Pharmacology, Faculty of Veterinary Medicine, Kafr El-Shikh University, Kafr El-Shikh 33516, Egypt.
J Bioenerg Biomembr. 2010 Oct;42(5):361-9. doi: 10.1007/s10863-010-9304-9. Epub 2010 Aug 17.
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.
核苷二磷酸激酶（NDKs）在维持细胞内能量资源以及核苷酸池的平衡方面发挥着关键作用。最近，由于 NDKs 在激活各种化疗药物方面的作用，人们对其关注度有所提高。不同核苷酸与 Pf 疟原虫 NDK 的结合亲和力按以下顺序变化：ADP~GDP>dGDP>dADP>dTDP>CDP>dCDP>UDP。嘌呤核苷酸的结合比嘧啶核苷酸更强。此外，PfNDK 对核糖核苷酸的偏好程度高于脱氧核糖核苷酸。嘧啶的负自由能比嘌呤低。所有核苷酸的相互作用都表现出有利的焓变和熵变。然而，焓变是嘌呤核苷酸的主要驱动力，而熵变则是嘧啶的主要驱动力。有趣的是，TDP 表现出明显的亲和力和更有利的焓变以及较小的熵变。总之，核苷酸的大小是 PfNDK 配体亲和力的关键因素。
