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Structure of Nampt/PBEF/visfatin, a mammalian NAD+ biosynthetic enzyme

Nature Structural & Molecular Biology volume 13, pages 661–662 (2006)Cite this article

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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Figure 1: Comparison of mouse Nampt with other type II phosphoribosyltransferases, with enzyme monomers in violet or green and substrate carbons in yellow.
Figure 2: Active site of Nampt complexed with NMN.

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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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Authors and Affiliations

  1. Department of Biophysics and Biophysical Chemistry, Johns Hopkins University School of Medicine, 725 N. Wolfe St., Baltimore, 21205, Maryland, USA

    Tao Wang, Xiangbin Zhang, Poonam Bheda & Cynthia Wolberger

  2. Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, 725 N. Wolfe St., Baltimore, 21205, Maryland, USA

    Tao Wang, Xiangbin Zhang & Cynthia Wolberger

  3. Department of Molecular Biology and Pharmacology, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, 63110, Missouri, USA

    Javier R Revollo & Shin-ichiro Imai

Authors
  1. Tao Wang
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Correspondence to Cynthia Wolberger.

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Supplementary information

Supplementary Fig. 1

ATP hydrolysis and autophosphorylation by Nampt (PDF 24 kb)

Supplementary Fig. 2 (PDF 70 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)

Supplementary Methods (PDF 71 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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