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NME3: Human Nucleoside-diphosphate Kinase 3

PDB entry: 1ZS6

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Protein expressed in non-metastatic cell 3 (NME3), also known as nucleoside-diphosphate kinase, nucleoside 5\'-diphosphate phosphotransferase and NM23, catalyzes the ATP gamma phosphate transfer to the NDP beta phosphate via a ping-pong mechanism, using a phosphorylated histidine intermediate in the active-site: ATP + nucleoside diphosphate <=> ADP + nucleoside triphosphate. Thus, the enzyme participates in synthesis of the nucleoside triphosphates, and can produce precursors for RNA and DNA synthesis. The involvement of NME proteins in complex regulatory processes has inspired interest, especially after their identification as critical factors for carcinomas metastasis. Eight isoforms in human have been documented, four of which (NME1 - NME4) reveal much higher sequence conservation than the other four (NME5 - NME8). NME1 and NME2 isoforms have been extensively studied, as suppressor of the metastasis in some tumor types. Crystallographic and chromatographic data indicated that NME proteins are homohexamers with highly conserved sequence motif, NXXHG/ASD, in the active site.

We solved the structure of NME3, which shares 67 and 65% sequence identity to NME1 and NME2, respectively. The functional diversity of the enzyme is still not well understood and mainly related to its tissue and subcellular localization. Further structural and functional studies on NME3 and the other isoforms (NME5 - NME8) of the enzyme will advance the understanding of their roles in metastasis.

Materials and Methods