Abstract
Nicotinamide phosphoribosyltransferase (Nampt) synthesizes nicotinamide mononucleotide (NMN) from nicotinamide in a mammalian NAD+ biosynthetic pathway and is required for SirT1 activity in vivo. Nampt has also been presumed to be a cytokine (PBEF) or a hormone (visfatin). The crystal structure of Nampt in the presence and absence of NMN shows that Nampt is a dimeric type II phosphoribosyltransferase and provides insights into the enzymatic mechanism.
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Acknowledgements
We thank the staff at GM/CA-CAT at the Advanced Photon Source, which is funded in part by the US National Cancer Institute (Y1-CO-1020) and the US National Institute of General Medical Sciences (Y1-GM-1104). J.R.R. is a fellow supported by the Lucille P. Markey Special Emphasis Pathway in Human Pathology. S.I. is an Ellison Medical Foundation Scholar in Aging.
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Supplementary information
Supplementary Fig. 1
ATP hydrolysis and autophosphorylation by Nampt (PDF 24 kb)
Supplementary Table 1
Data collection, phasing, and refinement statistics (PDF 52 kb)
Supplementary Table 2
Kinetics parameters of His-tagged Nampt and Nampt mutants (PDF 24 kb)
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Wang, T., Zhang, X., Bheda, P. et al. Structure of Nampt/PBEF/visfatin, a mammalian NAD+ biosynthetic enzyme. Nat Struct Mol Biol 13, 661–662 (2006). https://doi.org/10.1038/nsmb1114
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DOI: https://doi.org/10.1038/nsmb1114
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