Structural characterization of a human cytosolic NMN/NaMN adenylyltransferase and implication in human NAD biosynthesis
Open accessAbstract
Pyridine dinucleotides (NAD and NADP) are ubiquitous cofactors involved in hundreds of redox reactions essential for the energy transduction and metabolism in all living cells. In addition, NAD also serves as a substrate for ADP-ribosylation of a number of nuclear proteins, for silent information regulator 2 (Sir2)-like histone deacetylase that is involved in gene silencing regulation, and for cyclic ADP ribose (cADPR)-dependent Ca(2+) signaling. Pyridine nucleotide adenylyltransferase (PNAT) is an indispensable central enzyme in the NAD biosynthesis pathways catalyzing the condensation of pyridine mononucleotide (NMN or NaMN) with the AMP moiety of ATP to form NAD (or NaAD). Here we report the identification and structural characterization of a novel human PNAT (hsPNAT-3) that is located in the cytoplasm and mitochondria. Its subcellular localization and tissue distribution are distinct from the previously identified human nuclear PNAT-1 and PNAT-2. Detailed structural analysis of PNAT-3 in its apo form and in complex with its substrate(s) or product revealed the catalytic mechanism of the enzyme. The characterization of the cytosolic human PNAT-3 provided compelling evidence that the final steps of NAD biosynthesis pathways may exist in mammalian cytoplasm and mitochondria, potentially contributing to their NAD/NADP pool.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The differential subcellular distribution of NMNAT1, NMNAT2 and NMNAT3 is consistent with previous observations that found NMNAT1 in the nucleus, NMNAT2 in the Golgi complex and neurites and NMNAT3 in the mitochondria.
“This differential subcellular distribution is consistent with previous observations that found NMNAT1 in the nucleus, NMNAT2 in the Golgi complex and neurites and NMNAT3 in the mitochondria (25,26,55,56).”
From CREB-activity and nmnat2 transcription are down-regulated prior to neurodegeneration, while NMNAT2 over-expression is neuroprotective, in a mouse model of human tauopathy (2012) · cites this paper as [26]
In Results and Discussion (page not supplied), the paper reports nuclear hsPNAT-1 and mitochondrial hsPNAT-3. It does not place hsPNAT-2 in the Golgi complex or neurites; it says its exact cellular location remains to be determined. (LLM, conf=0.91)
Experimental — accuracy not yet measuredThree mammalian homologs NMNAT1-3 have been identified, with NMNAT2 being the most labile of the three isoforms with a half-life of approximately 4 h.
“Three mammalian homologs, NMNAT1 -3, have been identified (24)(25)(26), with NMNAT2 (nicotinamide mononucleotide adenylyltransferase 2) being the most labile of the three isoforms with a half-life of ,4 h (27).”
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Gapped BLAST and PSI-BLAST: a new generation of protein database search programs
Altschul, S. (1997) · Nucleic Acids Research · doi:10.1093/nar/25.17.3389 · Cited by 73,302 · see citing works
[20] Processing of X-ray diffraction data collected in oscillation mode
Otwinowski, Z., & Minor, W. (1997) · Methods in Enzymology · doi:10.1016/s0076-6879(97)76066-x · Cited by 33,475 · see citing works
Crystallography & NMR System: A New Software Suite for Macromolecular Structure Determination
Brünger, A. T., Adams, P. D., Clore, G. M., DeLano, W. L., Gros, P., Grosse‐Kunstleve, R. W., Jiang, J., Kuszewski, J. J., Nilges, M., Pannu, N., et al. (1998) · Acta Crystallographica Section D Biological Crystallography · doi:10.1107/s0907444998003254 · Cited by 15,720 · see citing works
MOLSCRIPT: a program to produce both detailed and schematic plots of protein structures
Kraulis, P. J. (1991) · Journal of Applied Crystallography · doi:10.1107/s0021889891004399 · Cited by 14,011 · see citing works
Jones, T. A., Zou, J.-Y., Cowan, S. W., & Kjeldgaard, M. (1991) · Acta Crystallographica Section A Foundations of Crystallography · doi:10.1107/s0108767390010224 · Cited by 12,650 · see citing works
An extensively modified version of MolScript that includes greatly enhanced coloring capabilities
Esnouf, R. M. (1997) · Journal of Molecular Graphics and Modelling · doi:10.1016/s1093-3263(97)00021-1 · Cited by 1,710 · see citing works
Sir2 links chromatin silencing, metabolism, and agingPreprint
Guarente, L. (2000) · Genes & Development · doi:10.1101/gad.14.9.1021 · Cited by 718 · see citing works
Di Lisa, F., Menabò, R., Canton, M., Barile, M., & Bernardi, P. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m006825200 · Cited by 678 · see citing works
Wallerian degeneration of injured axons and synapses is delayed by a Ube4b/Nmnat chimeric gene
Mack, T. G. A., Reiner, M., Beirowski, B., Mi, W., Emanuelli, M., Wagner, D., Thomson, D., Gillingwater, T., Court, F., Conforti, L., et al. (2001) · Nature Neuroscience · doi:10.1038/nn770 · Cited by 611 · see citing works
Functions of poly(ADP-ribose) polymerase (PARP) in DNA repair, genomic integrity and cell death
Herceg, Z., & Wang, Z. (2001) · Mutation research. Fundamental and molecular mechanisms of mutagenesis · doi:10.1016/s0027-5107(01)00111-7 · Cited by 489 · see citing works
Physiological functions of cyclic ADP-ribose and NAADP as calcium messengers
Lee, H. C. (2001) · Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev.pharmtox.41.1.317 · Cited by 433 · see citing works
New functions of a long‐known molecule
Ziegler, M. (2000) · European Journal of Biochemistry · doi:10.1046/j.1432-1327.2000.01187.x · Cited by 289 · see citing works
From Genetic Footprinting to Antimicrobial Drug Targets: Examples in Cofactor Biosynthetic Pathways
Gerdes, S., Scholle, M. D., D’Souza, M., Bernal, A., Baev, M. V., Farrell, M., Kurnasov, O. V., Daugherty, M. D., Mseeh, F., Polanuyer, B. M., et al. (2002) · Journal of Bacteriology · doi:10.1128/jb.184.16.4555-4572.2002 · Cited by 282 · see citing works
Self-citationConforti, L., Tarlton, A., Mack, T. G. A., Mi, W., Buckmaster, E. A., Wagner, D., Perry, V. H., & Coleman, M. P. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.97.21.11377 · Cited by 251 · see citing works
Magni, G., Amici, A., Emanuelli, M., Raffaelli, N., & Ruggieri, S. (1999) · Advances in enzymology and related areas of molecular biology/Advances in enzymology and related subjects · doi:10.1002/9780470123195.ch5 · Cited by 235 · see citing works
Tischler, M. E., Friedrichs, D., Coll, K. E., & WILLIAMSON, J. R. (1977) · Archives of Biochemistry and Biophysics · doi:10.1016/0003-9861(77)90346-0 · Cited by 209 · see citing works
Emanuelli, M., Carnevali, F., Saccucci, F., Pierella, F., Amici, A., Raffaelli, N., & Magni, G. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m008700200 · Cited by 189 · see citing works
Branster, M. V., & Morton, R. K. (1956) · Biochemical Journal · doi:10.1042/bj0630640 · Cited by 174 · see citing works
Structural and Functional Characterization of Human NAD Kinase
Lerner, F., Niere, M., Ludwig, A., & Ziegler, M. (2001) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.2001.5735 · Cited by 172 · see citing works
Pathophysiological relevance of mitochondria in NAD+ metabolism
Lisa, F. D., & Ziegler, M. (2001) · FEBS Letters · doi:10.1016/s0014-5793(01)02198-6 · Cited by 161 · see citing works
Enzymatic activities of Sir2 and chromatin silencing
Moazed, D. (2001) · Current Opinion in Cell Biology · doi:10.1016/s0955-0674(00)00202-7 · Cited by 160 · see citing works
Pyridine nucleotide coenzymes. Chemical, biochemical and medical aspects
(1988) · Analytical Biochemistry · doi:10.1016/0003-2697(88)90348-x · Cited by 145 · see citing works
The biosynthesis of nicotinamide adenine dinucleotides in bacteria
Begley, T. P., Kinsland, C. L., Mehl, R. A., Osterman, A. L., & Dorrestein, P. C. (2001) · Vitamins and hormones · doi:10.1016/s0083-6729(01)61003-3 · Cited by 143 · see citing works
Self-citationSchweiger, M., Hennig, K., Lerner, F., Niere, M., Hirsch‐Kauffmann, M., Specht, T., Weise, C., Oei, S. L., & Ziegler, M. (2001) · FEBS Letters · doi:10.1016/s0014-5793(01)02180-9 · Cited by 137 · see citing works
Identification of a novel human nicotinamide mononucleotide adenylyltransferase
Raffaelli, N., Sorci, L., Amici, A., Emanuelli, M., Mazzola, F., & Magni, G. (2002) · Biochemical and Biophysical Research Communications · doi:10.1016/s0006-291x(02)02285-4 · Cited by 127 · see citing works
A cellular survival switch: poly(ADP‐ribosyl)ation stimulates DNA repair and silences transcription
Ziegler, M., & Oei, S. L. (2001) · BioEssays · doi:10.1002/bies.1074 · Cited by 125 · see citing works
Enzymic Synthesis of Coenzyme I in Relation to Chemical Control of Cell Growth
Morton, R. K. (1958) · Nature · doi:10.1038/181540a0 · Cited by 103 · see citing works
Bürkle, A. (2001) · Cancer Letters · doi:10.1016/s0304-3835(00)00694-7 · Cited by 94 · see citing works
Peer Bork, B., Holm, L., Koonin, E. V., & Sander, C. (1995) · Proteins Structure Function and Bioinformatics · doi:10.1002/prot.340220306 · Cited by 87 · see citing works
Kurnasov, O. V., Polanuyer, B. M., Ananta, S., Sloutsky, R., Tam, A., Gerdes, S., & Osterman, A. L. (2002) · Journal of Bacteriology · doi:10.1128/jb.184.24.6906-6917.2002 · Cited by 87 · see citing works
Self-citationStructure of Human Nicotinamide/Nicotinic Acid Mononucleotide Adenylyltransferase
Zhou, T., Kurnasov, O. V., Tomchick, D. R., Binns, D. D., Grishin, N. V., Márquez, V. E., Osterman, A. L., & Zhang, H. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m111469200 · Cited by 86 · see citing works
Self-citationStructure of Human NMN Adenylyltransferase
Garavaglia, S., D’Angelo, I., Emanuelli, M., Carnevali, F., Pierella, F., Magni, G., & Rizzi, M. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m111589200 · Cited by 85 · see citing works
Assay methods for nicotinamide mononucleotide adenylyltransferase of wide applicability.
Balducci, E., Emanuelli, M., Raffaelli, N., Ruggieri, S., Amici, A., Magni, G., Orsomando, G., Polzonetti, V., & Natalini, P. (1995) · Analytical Biochemistry · doi:10.1006/abio.1995.1315 · Cited by 79 · see citing works
Izard, T. (2002) · Journal of Molecular Biology · doi:10.1006/jmbi.2001.5272 · Cited by 78 · see citing works
Structure of nicotinamide mononucleotide adenylyltransferase: a key enzyme in NAD+ biosynthesis
D’Angelo, I., Raffaelli, N., Dabusti, V., Lorenzi, T., Magni, G., & Rizzi, M. (2000) · Structure · doi:10.1016/s0969-2126(00)00190-8 · Cited by 76 · see citing works
Zhang, H., Zhou, T., Kurnasov, O. V., Cheek, S., Grishin, N. V., & Osterman, A. L. (2002) · Structure · doi:10.1016/s0969-2126(01)00693-1 · Cited by 74 · see citing works
Self-citationCooney, D. A., Jayaram, H. N., Glazer, R. I., Kelley, J. A., Márquez, V. E., Gebeyehu, G., Cott, A. C. V., Zwelling, L. A., & Johns, D. G. (1983) · Advances in Enzyme Regulation · doi:10.1016/0065-2571(83)90019-5 · Cited by 56 · see citing works
Olland, A. M., Underwood, K. W., Czerwiński, R., Lo, M.-C., AULABAUGH, A. E., Bard, J., Stahl, M., Somers, W. S., Sullivan, F. X., & Chopra, R. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m109670200 · Cited by 55 · see citing works
Insights into Ligand Binding and Catalysis of a Central Step in NAD+ Synthesis
Saridakis, V., Christendat, D., Kimber, M. S., Dharamsi, A., Edwards, A. M., & PAI, E. F. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m008810200 · Cited by 54 · see citing works
Guse, A. H. (2002) · Current Molecular Medicine · doi:10.2174/1566524024605707 · Cited by 53 · see citing works
Barile, M., Passarella, S., Danese, G., & Quagliariello, E. (1996) · PubMed · Cited by 52 · see citing works
Crystal Structure of Haemophilus influenzae NadR Protein
Singh, S. K., Kurnasov, O. V., Chen, B., Robinson, H. H., Grishin, N. V., Osterman, A. L., & Zhang, H. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m204368200 · Cited by 50 · see citing works
Self-citationCrystal structure of human nicotinamide mononucleotide adenylyltransferase in complex with NMN
Werner, E., Ziegler, M., Lerner, F., Schweiger, M., & Heinemann, U. (2002) · FEBS Letters · doi:10.1016/s0014-5793(02)02556-5 · Cited by 44 · see citing works
Emanuelli, M., Natalini, P., Raffaelli, N., Ruggieri, S., Vita, A., & Magni, G. (1992) · Archives of Biochemistry and Biophysics · doi:10.1016/0003-9861(92)90089-f · Cited by 41 · see citing works
Ruggieri, S., Gregori, L. L., Natalini, P., Vita, A., Emanuelli, M., Raffaelli, N., & Magni, G. (1990) · Biochemistry · doi:10.1021/bi00462a010 · Cited by 32 · see citing works
Mechanism of resistance to tiazofurin in hepatoma 3924A
Jayaram, H. N., Pillwein, K., Lui, M. S., Faderan, M. A., & Weber, G. (1986) · Biochemical Pharmacology · doi:10.1016/0006-2952(86)90352-7 · Cited by 30 · see citing works
NMN adenylyltransferase from bull testis: purification and properties
Balducci, E., Orsomando, G., Polzonetti, V., Vita, A., Emanuelli, M., Raffaelli, N., Ruggieri, S., Magni, G., & Natalini, P. (1995) · Biochemical Journal · doi:10.1042/bj3100395 · Cited by 28 · see citing works
Nicotinamide mononucleotide adenylyltransferase, a nonhistone chromatin protein
Cantarow, W. D., & Stollar, B. D. (1977) · Archives of Biochemistry and Biophysics · doi:10.1016/0003-9861(77)90004-2 · Cited by 21 · see citing works
Enzyme Activities Leading to NAD Synthesis in Human Lymphocytes
Sestini, S., Jacomelli, G., Pescaglini, M., Micheli, V., & Pompucci, G. (2000) · Archives of Biochemistry and Biophysics · doi:10.1006/abbi.2000.1888 · Cited by 20 · see citing works
NMN Adenylyltransferase: Its Association with Chromatin and with Poly(ADP‐ribose) Polymerase
Uhr, M. L., & Smulson, M. E. (1982) · European Journal of Biochemistry · doi:10.1111/j.1432-1033.1982.tb06983.x · Cited by 20 · see citing works
Nuclear matrix-associated NMN adenylyltransferase activity in human placenta
Balducci, E., Emanuelli, M., Magni, G., Raffaelli, N., Ruggieri, S., Vita, A., & Natalini, P. (1992) · Biochemical and Biophysical Research Communications · doi:10.1016/0006-291x(92)90211-3 · Cited by 19 · see citing works
The Stereochemical Course of Nucleotidyl Transfer Catalysed by NAD Pyrophosphorylase
Lowe, G. M., & Tansley, G. (1983) · European Journal of Biochemistry · doi:10.1111/j.1432-1033.1983.tb07334.x · Cited by 18 · see citing works
Berger, S. J., & DeVries, G. W. (1982) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.1982.tb08704.x · Cited by 7 · see citing works
Flagged first, then by citations
2 of the 55 references couldn’t be matched to a known paper.
Research works printed but not linked: 1
- Conforti, L., Tarlton, A., Mack, T. G., Mi, W., Buckmaster, E. A., Wagner, D., Perry, V. H., and Coleman, M. P. (2000) Proc. Natl. Acad. Sci. U. S. A. 97, 11377-11382
Cited by
Sorted by citations
Cantó, C., Menzies, K. J., & Auwerx, J. (2015) · Cell Metabolism · doi:10.1016/j.cmet.2015.05.023 · Cited by 1,648 · see citing works
NAD+ metabolism and its roles in cellular processes during ageing
Covarrubias, A. J., Perrone, R., Grozio, A., & Verdin, E. (2021) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-020-00313-x · Cited by 1,617 · see citing works
NAD <sup>+</sup> in aging, metabolism, and neurodegeneration
Verdin, E. (2015) · Science · doi:10.1126/science.aac4854 · Cited by 1,319 · see citing works
NAD(H) and NADP(H) Redox Couples and Cellular Energy Metabolism
Xiao, W., Wang, R., Handy, D. E., & Loscalzo, J. (2017) · Antioxidants and Redox Signaling · doi:10.1089/ars.2017.7216 · Cited by 1,074 · see citing works
The secret life of NAD+: an old metabolite controlling new metabolic signaling pathways
Houtkooper, R. H., Cantó, C., Wanders, R. J., & Auwerx, J. (2010) · Endocrine Reviews · doi:10.1210/er.2009-0026 · Cited by 899 · see citing works
SIRT5 deacetylates carbamoyl phosphate synthetase 1 and regulates the urea cycle
Nakagawa, T., Lomb, D. J., Haigis, M. C., & Guarente, L. (2009) · Cell · doi:10.1016/j.cell.2009.02.026 · Cited by 787 · see citing works
PARPs and ADP-ribosylation: recent advances linking molecular functions to biological outcomes
Gupte, R., Liu, Z., & Kraus, W. L. (2017) · Genes & Development · doi:10.1101/gad.291518.116 · Cited by 681 · see citing works
Nuclear ADP-Ribosylation Reactions in Mammalian Cells: Where Are We Today and Where Are We Going?
Hassa, P. O., Haenni, S. S., Elser, M., & Hottiger, M. O. (2006) · Microbiology and Molecular Biology Reviews · doi:10.1128/mmbr.00040-05 · Cited by 682 · see citing works
NAD+ homeostasis in health and disease
Katsyuba, E., Romani, M., Hofer, D., & Auwerx, J. (2020) · Nature Metabolism · doi:10.1038/s42255-019-0161-5 · Cited by 627 · see citing works
Berger, F., Lau, C., Dahlmann, M., & Ziegler, M. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m508660200 · Cited by 508 · see citing works
The new life of a centenarian: signalling functions of NAD(P)
Berger, F. (2004) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2004.01.007 · Cited by 489 · see citing works
Endogenous Nmnat2 Is an Essential Survival Factor for Maintenance of Healthy Axons
Gilley, J., & Coleman, M. P. (2010) · PLoS Biology · doi:10.1371/journal.pbio.1000300 · Cited by 472 · see citing works
Murphy, M. P. (2011) · Antioxidants and Redox Signaling · doi:10.1089/ars.2011.4289 · Cited by 341 · see citing works
Protein acetylation in metabolism – metabolites and cofactors
Menzies, K. J., Zhang, H., Katsyuba, E., & Auwerx, J. (2016) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2015.181 · Cited by 331 · see citing works
Self-citationEnzymology of NAD+ homeostasis in man
Magni, G., Amici, A., Emanuelli, M., Orsomando, G., Raffaelli, N., & Ruggieri, S. (2004) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-003-3161-1 · Cited by 289 · see citing works
Reconstructing eukaryotic NAD metabolism.
Rongvaux, A., Andris, F., Gool, F. V., & Leo, O. (2003) · Bioessays · doi:10.1002/bies.10297 · Cited by 284 · see citing works
Sasaki, Y., Araki, T., & Milbrandt, J. (2006) · The Journal of Neuroscience · doi:10.1523/jneurosci.2320-06.2006 · Cited by 269 · see citing works
NAD metabolism: Implications in aging and longevity
Yaku, K., Okabe, K., & Nakagawa, T. (2018) · Ageing Research Reviews · doi:10.1016/j.arr.2018.05.006 · Cited by 269 · see citing works
Identification of the Mitochondrial NAD+ Transporter in Saccharomyces cerevisiae
Todisco, S., Agrimi, G., Castegna, A., & Palmieri, F. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m510425200 · Cited by 223 · see citing works
Modulating NAD+ metabolism, from bench to bedside
Katsyuba, E., & Auwerx, J. H. (2017) · The EMBO Journal · doi:10.15252/embj.201797135 · Cited by 224 · see citing works
The Highwire Ubiquitin Ligase Promotes Axonal Degeneration by Tuning Levels of Nmnat Protein
Xiong, X., Hao, Y., Sun, K., Li, J., Li, X., Mishra, B., Soppina, P., Wu, C., Hume, R. I., & Collins, C. A. (2012) · PLoS Biology · doi:10.1371/journal.pbio.1001440 · Cited by 200 · see citing works
NAD synthase NMNAT acts as a chaperone to protect against neurodegeneration
Zhai, R. G., Zhang, F., Hiesinger, P. R., Cao, Y., Haueter, C. M., & Bellen, H. J. (2008) · Nature · doi:10.1038/nature06721 · Cited by 201 · see citing works
Drosophila NMNAT Maintains Neural Integrity Independent of Its NAD Synthesis Activity
Zhai, R. G., Cao, Y., Hiesinger, P. R., Zhou, Y., Mehta, S. Q., Schulze, K. L., Verstreken, P., & Bellen, H. J. (2006) · PLoS Biology · doi:10.1371/journal.pbio.0040416 · Cited by 166 · see citing works
Metabolic Profiling of Alternative NAD Biosynthetic Routes in Mouse Tissues
Mori, V., Amici, A., Mazzola, F., Stefano, M. D., Conforti, L., Magni, G., Ruggieri, S., Raffaelli, N., & Orsomando, G. (2014) · PLoS ONE · doi:10.1371/journal.pone.0113939 · Cited by 158 · see citing works
A Genomewide Screen for Late-Onset Alzheimer Disease in a Genetically Isolated Dutch Population
Liu, F., Arias-Vásquez, A., Sleegers, K., Aulchenko, Y. S., Kayser, M., Sanchez-Juan, P., Feng, B.-J., Bertoli-Avella, A. M., van Swieten, J., Axenovich, T. I., et al. (2007) · The American Journal of Human Genetics · doi:10.1086/518720 · Cited by 156 · see citing works
Yahata, N., Yuasa, S., & Araki, T. (2009) · The Journal of Neuroscience · doi:10.1523/jneurosci.4304-08.2009 · Cited by 154 · see citing works
“, NMNAT1 and NMNAT3, either of which are unexpressed in neurons) (Emanuelli et al., 2001; Zhang et al., 2003).”
BackgroundInfluentialThe role of NAD+ metabolism and its modulation of mitochondria in aging and disease
Yusri, K., Jose, S., Vermeulen, K. S., Tan, T. C. M., & Sorrentino, V. (2025) · npj Metabolic Health and Disease · doi:10.1038/s44324-025-00067-0 · Cited by 171 · see citing works
New Facets in the Regulation of Gene Expression by ADP-Ribosylation and Poly(ADP-ribose) Polymerases
Ryu, K. W., Kim, D.-S., & Kraus, W. L. (2015) · Chemical Reviews · doi:10.1021/cr5004248 · Cited by 147 · see citing works
NAD – new roles in signalling and gene regulation in plants
Hunt, L., Lerner, F., & Ziegler, M. (2004) · New Phytologist · doi:10.1111/j.1469-8137.2004.01087.x · Cited by 139 · see citing works
Cambronne, X. A., & Kraus, W. L. (2020) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2020.05.010 · Cited by 137 · see citing works
Preclinical and clinical evidence of NAD+ precursors in health, disease, and ageing
Reiten, O. K., Wilvang, M. A., Mitchell, S. J., Hu, Z., & Fang, E. F. (2021) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2021.111567 · Cited by 133 · see citing works
The NMN/NaMN adenylyltransferase (NMNAT) protein family
Lau, C. (2009) · Frontiers in bioscience · doi:10.2741/3252 · Cited by 132 · see citing works
Kirkland, J. B., & Meyer‐Ficca, M. L. (2018) · Advances in food and nutrition research · doi:10.1016/bs.afnr.2017.11.003 · Cited by 134 · see citing works
Burgos, E. S., & Schramm, V. L. (2008) · Biochemistry · doi:10.1021/bi801198m · Cited by 123 · see citing works
Nicotinamidase participates in the salvage pathway of NAD biosynthesis in Arabidopsis
Wang, G., & Pichersky, E. (2007) · The Plant Journal · doi:10.1111/j.1365-313x.2006.03013.x · Cited by 116 · see citing works
Ashihara, H., Ludwig, I. A., Katahira, R., Yokota, T., Fujimura, T., & Crozier, A. (2015) · Phytochemistry Reviews · doi:10.1007/s11101-014-9375-z · Cited by 110 · see citing works
Interplay between compartmentalized NAD + synthesis and consumption: a focus on the PARP familyPreprint
Cohen, M. S. (2020) · Genes & Development · doi:10.1101/gad.335109.119 · Cited by 109 · see citing works
NAD and ADP ‐ribose metabolism in mitochondria
Dölle, C., Rack, J. G. M., & Ziegler, M. (2013) · FEBS Journal · doi:10.1111/febs.12304 · Cited by 108 · see citing works
Ljungberg, M. C., Ali, Y. O., Zhu, J., Wu, C.-S., Oka, K., Zhai, R. G., & Lu, H.-C. (2012) · Human Molecular Genetics · doi:10.1093/hmg/ddr492 · Cited by 107 · see citing works
Axonal energy metabolism, and the effects in aging and neurodegenerative diseases
Yang, S., Park, J. H., & Lu, H.-C. (2023) · Molecular Neurodegeneration · doi:10.1186/s13024-023-00634-3 · Cited by 94 · see citing works
Enzymology of mammalian NAD metabolism in health and disease
Magni, G. (2008) · Frontiers in bioscience · doi:10.2741/3143 · Cited by 93 · see citing works
Mayer, P. R., Huang, N., Dewey, C. M., Dries, D. R., Zhang, H., & Yu, G. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.178913 · Cited by 82 · see citing works
Self-citationNicotinamide/nicotinic acid mononucleotide adenylyltransferase, new insights into an ancient enzyme
Zhai, R. G., Rizzi, M., & Garavaglia, S. (2009) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-009-0047-x · Cited by 88 · see citing works
NMNAT Expression and its Relation to NAD Metabolism
Jayaram, H. N., Kusumanchi, P., & Yalowitz, J. A. (2011) · Current Medicinal Chemistry · doi:10.2174/092986711795590138 · Cited by 89 · see citing works
Metabolic and Bactericidal Effects of Targeted Suppression of NadD and NadE Enzymes in Mycobacteria
Rodionova, I. A., Schuster, B. M., Guinn, K. M., Sorci, L., Scott, D. A., Li, X., Kheterpal, I., Shoen, C. M., Cynamon, M. H., Locher, C. P., et al. (2014) · mBio · doi:10.1128/mbio.00747-13 · Cited by 82 · see citing works
Self-citationNAD Biosynthesis in Humans - Enzymes, Metabolites and Therapeutic Aspects
Dölle, C., Skoge, R. H., VanLinden, M. R., & Ziegler, M. (2013) · Current Topics in Medicinal Chemistry · doi:10.2174/15680266113136660206 · Cited by 78 · see citing works
Identification of the nicotinamide salvage pathway as a new toxification route for antimetabolites
Buonvicino, D., Mazzola, F., Zamporlini, F., Resta, F., Ranieri, G., Camaioni, E., Muzzi, M., Zecchi, R., Pieraccini, G., Dölle, C., et al. (2018) · Cell Chemical Biology · doi:10.1016/j.chembiol.2018.01.012 · Cited by 73 · see citing works
Sorci, L., Pan, Y., Eyobo, Y., Rodionova, I. A., Huang, N. N., Kurnasov, O. V., Zhong, S., MacKerell, A. D., Zhang, H., & Osterman, A. L. (2009) · Chemistry & Biology · doi:10.1016/j.chembiol.2009.07.006 · Cited by 72 · see citing works
Self-citationNmnat3 Is Dispensable in Mitochondrial NAD Level Maintenance In Vivo
Yamamoto, M., Hikosaka, K., Mahmood, A., Tobe, K., Shojaku, H., Inohara, H., & Nakagawa, T. (2016) · PLoS ONE · doi:10.1371/journal.pone.0147037 · Cited by 70 · see citing works
Lau, C., Dölle, C., Gossmann, T. I., Agledal, L., Niere, M., & Ziegler, M. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.107631 · Cited by 69 · see citing works
Felici, R., Lapucci, A., Ramazzotti, M., & Chiarugi, A. (2013) · PLoS ONE · doi:10.1371/journal.pone.0076938 · Cited by 63 · see citing works
Subcellular NAD+ pools are interconnected and buffered by mitochondrial NAD+
Høyland, L. E., VanLinden, M. R., Niere, M., Strømland, Ø., Sharma, S. A., Dietze, J., Tolås, I., Lucena, E., Bifulco, E., Sverkeli, L. J., et al. (2024) · Nature Metabolism · doi:10.1038/s42255-024-01174-w · Cited by 62 · see citing works
Diversification of NAD biological role : the importance of location
Stefano, M. D., & Conforti, L. (2013) · FEBS Journal · doi:10.1111/febs.12433 · Cited by 61 · see citing works
Hashida, S., Takahashi, H., Kawai‐Yamada, M., & Uchimiya, H. (2007) · The Plant Journal · doi:10.1111/j.1365-313x.2006.02989.x · Cited by 61 · see citing works
Lukacs, M., Gilley, J., Zhu, Y., Orsomando, G., Angeletti, C. A., Liu, J., Yang, X., Park, J., Hopkin, R. J., Coleman, M. P., et al. (2019) · Experimental Neurology · doi:10.1016/j.expneurol.2019.112961 · Cited by 61 · see citing works
Cell Biological Consequences of Mitochondrial NADH: Ubiquinone Oxidoreductase Deficiency
Smeitink, J. A. M., van den Heuvel, L., Koopman, W. J. H., Nijtmans, L. G. J., Ugalde, C., & Willems, P. H. G. M. (2004) · Current Neurovascular Research · doi:10.2174/1567202043480224 · Cited by 59 · see citing works
Impact of NAD+ metabolism on ovarian aging
Liang, J., Huang, F., Song, Z., Tang, R., Zhang, P., & Chen, R. (2023) · Immunity & Ageing · doi:10.1186/s12979-023-00398-w · Cited by 56 · see citing works
Comparative Genomics of NAD Biosynthesis in Cyanobacteria
Gerdes, S., Kurnasov, O. V., Shatalin, K. Y., Polanuyer, B. M., Sloutsky, R., Vonstein, V., Overbeek, R., & Osterman, A. L. (2006) · Journal of Bacteriology · doi:10.1128/jb.188.8.3012-3023.2006 · Cited by 53 · see citing works
Self-citationOwens, K., Park, J. H., Schuh, R. A., & Kristián, T. (2013) · Translational Stroke Research · doi:10.1007/s12975-013-0278-x · Cited by 53 · see citing works
NAD and axon degeneration: From the Wlds gene to neurochemistry
Wang, J., & He, Z. (2009) · Cell Adhesion & Migration · doi:10.4161/cam.3.1.7483 · Cited by 50 · see citing works
Parikh, S. L., & Schramm, V. L. (2004) · Biochemistry · doi:10.1021/bi035907z · Cited by 49 · see citing works
Roles of NAD + in Health and AgingPreprint
Lautrup, S., Hou, Y., Fang, E. F., & Bohr, V. A. (2023) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a041193 · Cited by 53 · see citing works
Ali, Y., Kitay, B. M., & Zhai, R. G. (2010) · Molecules · doi:10.3390/molecules15106859 · Cited by 47 · see citing works
Feng, Y., Yan, T., Zheng, J. H., Ge, X., Mu, Y., Zhang, Y., Wu, D., Du, J., & Zhai, Q. (2010) · Journal of Neuroscience Research · doi:10.1002/jnr.22498 · Cited by 46 · see citing works
Comparative genomics of NAD(P) biosynthesis and novel antibiotic drug targets
Bi, J., Wang, H., & Xie, J. (2010) · Journal of Cellular Physiology · doi:10.1002/jcp.22419 · Cited by 43 · see citing works
Lucena-Cacace, A., Umeda, M., Navas, L. E., & Carnero, A. (2019) · Frontiers in Oncology · doi:10.3389/fonc.2019.00292 · Cited by 43 · see citing works
Host–microbiome interactions in nicotinamide mononucleotide (NMN) deamidation
Kim, L., Chalmers, T. J., Madawala, R. J., Smith, G. C., Li, C., Das, A., Poon, E. W. K., Wang, J., Tucker, S. P., Sinclair, D. A., et al. (2023) · FEBS Letters · doi:10.1002/1873-3468.14698 · Cited by 41 · see citing works
A subsystems-based approach to the identification of drug targets in bacterial pathogens
Osterman, A. L., & Begley, T. P. (2007) · Birkhäuser Basel eBooks · doi:10.1007/978-3-7643-7567-6_6 · Cited by 39 · see citing works
Self-citationGenomics and Enzymology of NAD Biosynthesis
Sorci, L., Kurnasov, O. V., Rodionov, D. A., & Osterman, A. L. (2010) · Elsevier eBooks · doi:10.1016/b978-008045382-8.00138-6 · Cited by 39 · see citing works
Self-citationPetrelli, R., Felczak, K., & Cappellacci, L. (2011) · Current Medicinal Chemistry · doi:10.2174/092986711795590048 · Cited by 38 · see citing works
Nmnat2 Attenuates Tau Phosphorylation Through Activation of PP2A
Cheng, X., Zhao, K.-P., Jiang, X., Du, L., Li, X., Ma, Z., Yao, J., Luo, Y., Duan, D.-X., Wang, J., et al. (2013) · Journal of Alzheimer s Disease · doi:10.3233/jad-122173 · Cited by 37 · see citing works
Simultaneous Single-Sample Determination of NMNAT Isozyme Activities in Mouse Tissues
Orsomando, G., Cialabrini, L., Amici, A., Mazzola, F., Ruggieri, S., Conforti, L., Janečková, L., Coleman, M. P., & Magni, G. (2012) · PLoS ONE · doi:10.1371/journal.pone.0053271 · Cited by 36 · see citing works
Fortunato, C., Mazzola, F., & Raffaelli, N. (2021) · IUBMB Life · doi:10.1002/iub.2584 · Cited by 34 · see citing works
Huang, N. N., Sorci, L., Zhang, X., Brautigam, C. A., Li, X., Raffaelli, N., Magni, G., Grishin, N. V., Osterman, A. L., & Zhang, H. (2008) · Structure · doi:10.1016/j.str.2007.11.017 · Cited by 34 · see citing works
Self-citationJia, H., Yan, T., Feng, Y., Zeng, C., Shi, X., & Zhai, Q. (2006) · Neuroscience Letters · doi:10.1016/j.neulet.2006.11.067 · Cited by 33 · see citing works
Wang, X., Zhang, Z., Zhang, N., Li, H., Zhang, L., Baines, C. P., & Ding, S. (2019) · Journal of Neurochemistry · doi:10.1111/jnc.14878 · Cited by 33 · see citing works
Impaired Nicotinamide Adenine Dinucleotide Biosynthesis in the Kidney of Chronic Kidney Disease
Liu, X., Luo, D., Huang, S., Liu, S., Zhang, B., Wang, F., Lu, J., Chen, J., & Li, S. (2021) · Frontiers in Physiology · doi:10.3389/fphys.2021.723690 · Cited by 32 · see citing works
Stereoselective synthesis of nicotinamide β-riboside and nucleoside analogs
Franchetti, P., Pasqualini, M., Petrelli, R., Ricciutelli, M., Vita, P., & Cappellacci, L. (2004) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/j.bmcl.2004.06.093 · Cited by 32 · see citing works
Ma, X., Zhu, Y., Lu, J., Xie, J., Li, C. V., Shin, W. S., Qiang, J., Liu, J., Dou, S., Xiao, Y., et al. (2020) · eLife · doi:10.7554/elife.51859 · Cited by 29 · see citing works
Inhibitors of NAD+ Production in Cancer Treatment: State of the Art and Perspectives
Ghanem, M. S., Caffa, I., Monacelli, F., & Nencioni, A. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25042092 · Cited by 28 · see citing works
NAD metabolism in aging and cancer
Kincaid, J. W. R., & Berger, N. A. (2020) · Experimental Biology and Medicine · doi:10.1177/1535370220929287 · Cited by 28 · see citing works
Han, S., Forman, M. D., Loulakis, P., Rosner, M. H., Zhi, X., Wang, H., Danley, D. E., Yuan, W., Schafer, J. R., & Xu, Z. (2006) · Journal of Molecular Biology · doi:10.1016/j.jmb.2006.05.055 · Cited by 28 · see citing works
Unraveling the genes implicated in Alzheimer's disease
Giri, M., Shah, A., Upreti, B., & Rai, J. C. (2017) · Biomedical Reports · doi:10.3892/br.2017.927 · Cited by 25 · see citing works
Yoon, H., Kim, H., Mikami, B., & Suh, S. W. (2005) · Journal of Molecular Biology · doi:10.1016/j.jmb.2005.06.001 · Cited by 26 · see citing works
WldS, Nmnats and axon degeneration-progress in the past two decades
Feng, Y., Yan, T., He, Z., & Zhai, Q. (2010) · Protein & Cell · doi:10.1007/s13238-010-0021-2 · Cited by 25 · see citing works
Regulation of Cancer and Cancer-Related Genes via NAD +
Sharif, T., Martell, E., Dai, C., Ghassemi-Rad, M. S., Kennedy, B. E., Lee, P. W. K., & Gujar, S. A. (2018) · Antioxidants and Redox Signaling · doi:10.1089/ars.2017.7478 · Cited by 25 · see citing works
Stefano, M. D., Galassi, L., & Magni, G. (2010) · Blood Cells Molecules and Diseases · doi:10.1016/j.bcmd.2010.04.003 · Cited by 25 · see citing works
Kusumanchi, P., Zhang, Y., Jani, M., Jayaram, N. H., Khan, R. A., Tang, Y.-S., Antony, A. C., & Jayaram, H. N. (2013) · Cancer Gene Therapy · doi:10.1038/cgt.2013.33 · Cited by 24 · see citing works
Brunetti, L., Stefano, M. D., Ruggieri, S., Cimadamore, F., & Magni, G. (2010) · Protein Science · doi:10.1002/pro.526 · Cited by 23 · see citing works
A Panoramic Overview of Mitochondria and Mitochondrial Redox Biology
Kim, A. (2014) · Toxicological Research · doi:10.5487/tr.2014.30.4.221 · Cited by 22 · see citing works
NMNAT2: An important metabolic enzyme affecting the disease progression
Li, W., Gao, M., Hu, C., Chen, X., & Zhou, Y. (2022) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2022.114143 · Cited by 21 · see citing works
Sershon, V. C., Santarsiero, B. D., & Mesecar, A. D. (2008) · Journal of Molecular Biology · doi:10.1016/j.jmb.2008.10.037 · Cited by 20 · see citing works
Anterograde regulation of mitochondrial genes and FGF21 signaling by hepatic LSD1
Cao, Y., Tang, L., Du, K., Paraiso, K. D., Sun, Q., Liu, Z., Ye, X., Fang, Y., Yuan, F., Chen, H., et al. (2021) · JCI Insight · doi:10.1172/jci.insight.147692 · Cited by 18 · see citing works
Martino, C. D., & Pallotta, M. L. (2011) · Planta · doi:10.1007/s00425-011-1428-6 · Cited by 18 · see citing works
Hasegawa, K., Sakamaki, Y., Tamaki, M., & Wakino, S. (2022) · Scientific Reports · doi:10.1038/s41598-022-18147-2 · Cited by 17 · see citing works
Nmnat 1: a Security Guard of Retinal Ganglion Cells (RGCs) in Response to High Glucose Stress
Zhou, R., Shen, Y., Yao, J., Yang, H., Shan, K., Li, X., Jiang, Q. L., & Yan, B. (2016) · Cellular Physiology and Biochemistry · doi:10.1159/000445576 · Cited by 17 · see citing works
Felici, R., Lapucci, A., Ramazzotti, M., & Chiarugi, A. (2013) · PLoS ONE · doi:10.1371/annotation/f5e6107f-a911-4c15-a881-7cb7e4946ff6 · Cited by 17 · see citing works
Wang, S., Han, J. D. J., Xia, J., Hu, Y., Shi, L., Ren, A., Zhu, J. K., & Zhao, M. (2020) · Applied Microbiology and Biotechnology · doi:10.1007/s00253-020-10763-0 · Cited by 13 · see citing works
Contreras-Rodríguez, L. E., Neme, R., & Ramírez-Hernández, M. H. (2015) · Protein Expression and Purification · doi:10.1016/j.pep.2015.08.022 · Cited by 13 · see citing works
Bathke, J., Fritz‐Wolf, K., Brandstädter, C., Burkhardt, A., Jortzik, E., Rahlfs, S., & Becker, K. (2016) · Journal of Molecular Biology · doi:10.1016/j.jmb.2016.10.023 · Cited by 10 · see citing works
- Authors
- Zhang, X., Kurnasov, O. V., Karthikeyan, S., Grishin, N. V., Osterman, A. L., & Zhang, H.
- Affiliations
- Howard Hughes Medical Institute (US)
- Igenbio (United States) (US)
- Corresponding author
- Zhang, Hong
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2003-04
- Volume
- 278
- Issue
- 15
- Pages
- 13503-13511
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2048878532
- Cited by
- 136
- References
- 55
- Citations by year
- 2026: 2 · 2025: 6 · 2024: 3 · 2023: 5 · 2022: 7 · 2021: 4 · 2020: 10 · 2019: 5 · 2018: 8 · 2017: 4 · 2016: 4 · 2015: 6 · 2014: 4 · 2013: 8 · 2012: 2
- FWCI
- 2.19
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- Welch Foundation
- McKnight Foundation
- National Institutes of Health
- National Institute of General Medical Sciences (R01GM065243, GM65243)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Biochemical and Molecular Research
- Health Sciences › Medicine › Geriatrics and Gerontology › Sirtuins and Resveratrol in Medicine
- Physical Sciences › Materials Science › Materials Chemistry › Enzyme Structure and Function
- Keywords
- NAD biosynthesis, NADPH, nicotinamide mononucleotide, enzyme structure, catalytic mechanism, subcellular localization, mitochondrial enzymes, cytosolic enzyme, ADP-ribosylation, cofactors
- MeSH terms
- Cell Line, Cytosol, HeLa Cells, Humans, Models, Molecular, NAD, Nicotinamide-Nucleotide Adenylyltransferase, Protein Conformation, Recombinant Proteins, Subcellular Fractions, Transfection, Tumor Cells, Cultured, Protein Structure, Secondary, Crystallography, X-Ray
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
