NDPKs

Nucleoside diphosphate kinases (NDPKs) are a family of enzymes that catalyze the transfer of a phosphate from nucleoside triphosphates (NTPs) to nucleoside diphosphates (NDPs), thereby helping maintain balanced pools of cellular nucleotides. The standard reaction can be described as NTP + NDP ⇌ NDP + NTP, enabling rapid interconversion among nucleotide triphosphates and diphosphates for various cellular needs, independent of the nucleotide base.

A hallmark of NDPKs is a conserved active site that contains a histidine residue forming a transient phosphohistidine intermediate during catalysis. The enzyme operates via a ping-pong mechanism: the histidine becomes phosphorylated and then transfers the phosphate to an NDP, regenerating the enzyme for another catalytic cycle. The histidine-based mechanism is characteristic across the family.

Diversity and distribution: NDPKs are widespread, found in bacteria, archaea, plants, and animals. In bacteria, a single ndk gene typically encodes the enzyme, while in animals multiple paralogs exist. In humans, the NME (NM23) gene family comprises several members (for example NME1–NME8) with distinct cellular localizations and regulatory properties, reflecting functional specialization.

Functions and roles: In addition to maintaining nucleotide pools, NDPKs participate in various cellular processes through phosphotransfer signaling. They are involved in microtubule dynamics, vesicle trafficking, and GTPase signaling, and may influence transcriptional regulation in certain contexts. Some NDPKs also exhibit chaperone-like activities or interact with signaling networks beyond metabolism.

Clinical and research relevance: NM23 family members have been studied for roles in cancer biology, notably NM23-H1 (NME1), historically described as a metastasis suppressor in several cancer types, though mechanisms are complex and context-dependent. Alterations in NDPK activity can impact cellular energy balance and signaling pathways, making them a subject of ongoing investigation.