7n29 | pdb_00007n29

Structure of NAD kinase

spinqualitylabelsall models 7n29, resolution 2.80Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 7n29 is a 4 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: NAD NonStd Res: MSE Activity: NAD(+) kinase, with EC number 2.7.1.23 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Disease [NAKD2_HUMAN] Progressive encephalopathy with leukodystrophy due to DECR deficiency. The disease is caused by variants affecting the gene represented in this entry. Function [NAKD2_HUMAN] Mitochondrial NAD(+) kinase that phosphorylates NAD(+) to yield NADP(+). Can use both ATP or inorganic polyphosphate as the phosphoryl donor. Also has weak NADH kinase activity in vitro; however NADH kinase activity is much weaker than the NAD(+) kinase activity and may not be relevant in vivo. Publication Abstract from PubMed All kingdoms of life produce essential nicotinamide dinucleotide NADP(H) using NAD kinases (NADKs). A panel of published NADK structures from bacteria, eukaryotic cytosol, and yeast mitochondria revealed similar tetrameric enzymes. Here, we present the 2.8-A structure of the human mitochondrial kinase NADK2 with a bound substrate, which is an exception to this uniformity, diverging both structurally and biochemically from NADKs. We show that NADK2 harbors a unique tetramer disruptor/dimerization element, which is conserved in mitochondrial kinases of animals (EMKA) and absent from other NADKs. EMKA stabilizes the NADK2 dimer but prevents further NADK2 oligomerization by blocking the tetramerization interface. This structural change bears functional consequences and alters the activation mechanism of the enzyme. Whereas tetrameric NADKs undergo cooperative activation via oligomerization, NADK2 is a constitutively active noncooperative dimer. Thus, our data point to a unique regulation of NADP(H) synthesis in animal mitochondria achieved via structural adaptation of the NADK2 kinase. Structure of human NADK2 reveals atypical assembly and regulation of NAD kinases from animal mitochondria.,Du J, Estrella M, Solorio-Kirpichyan K, Jeffrey PD, Korennykh A Proc Natl Acad Sci U S A. 2022 Jun 28;119(26):e2200923119. doi:, 10.1073/pnas.2200923119. Epub 2022 Jun 21. PMID:35733246 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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