Crystal structure of human nicotinamide mononucleotide adenylyltransferase in complex with NMN.
The final step in the biosynthesis of nicotinamide-adenine dinucleotide, a major coenzyme in cellular redox reactions and involved in intracellular signaling, is catalyzed by the enzyme nicotinamide mononucleotide adenylyltransferase (NMNAT). The X-ray structure of human NMNAT in complex with nicotinamide mononucleotide was solved by the single-wavelength anomalous dispersion method at a resolution of 2.9 A. Human NMNAT is a symmetric hexamer whose subunit is formed by a large six-stranded parallel beta-sheet with helices on both sides. Human NMNAT displays a different oligomerization compared to the archaeal enzyme. The protein-nicotinamide mononucleotide interaction pattern provides insight into ligand binding in the human enzyme.
Werner
Erik
E
Crystallography Group, Max Delbrück Center for Molecular Medicine, Robert-Rössle-Str. 10, D-13092, Berlin, Germany. ewe@mdc-berlin.de
Ziegler
Mathias
M
Lerner
Felicitas
F
Schweiger
Manfred
M
Heinemann
Udo
U
D000595:Amino Acid Sequence; D001665:Binding Sites; D018360:Crystallography, X-Ray; D006801:Humans; D046911:Macromolecular Substances; D017014:Methanobacterium / Q000201:enzymology / Q000235:genetics; D008969:Molecular Sequence Data; D009537:Nicotinamide Mononucleotide / Q000737:chemistry*; D009612:Nicotinamide-Nucleotide Adenylyltransferase / Q000737:chemistry* / Q000235:genetics; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D021122:Protein Subunits; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics; D017386:Sequence Homology, Amino Acid
D046911:Macromolecular Substances; D021122:Protein Subunits; D011994:Recombinant Proteins; D009537:Nicotinamide Mononucleotide; D009612:Nicotinamide-Nucleotide Adenylyltransferase