7N29

Structure of NAD kinase

Summary for 7N29

• Entry DOI: 10.2210/pdb7n29/pdb
• Descriptor: NAD kinase 2, mitochondrial, NICOTINAMIDE-ADENINE-DINUCLEOTIDE (3 entities in total)
• Functional Keywords: nad, atp, kinase, mitochondria, transferase
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 4
• Total formula weight: 183903.25

Authors

Du, J.,Estrella, M.A.,Jeffrey, P.D.,Korennykh, A.V. (deposition date: 2021-05-28, release date: 2022-05-04, Last modification date: 2024-10-30)

Primary citation

Du, J.,Estrella, M.,Solorio-Kirpichyan, K.,Jeffrey, P.D.,Korennykh, A.
Structure of human NADK2 reveals atypical assembly and regulation of NAD kinases from animal mitochondria.
Proc.Natl.Acad.Sci.USA, 119:e2200923119-e2200923119, 2022

PubMed Abstract: 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-Å 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 lement, which is conserved in itochondrial inases of nimals (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.

PubMed: 35733246
DOI: 10.1073/pnas.2200923119

Experimental method

X-RAY DIFFRACTION (2.8 Å)