skip to main content
OSTI.GOV title logo U.S. Department of Energy
Office of Scientific and Technical Information

Title: Crystallographic structure of a small molecule SIRT1 activator-enzyme complex


Citation Formats

Dai, Han, Case, April W., Riera, Thomas V., Considine, Thomas, Lee, Jessica E., Hamuro, Yoshitomo, Zhao, Huizhen, Jiang, Yong, Sweitzer, Sharon M., Pietrak, Beth, Schwartz, Benjamin, Blum, Charles A., Disch, Jeremy S., Caldwell, Richard, Szczepankiewicz, Bruce, Oalmann, Christopher, Yee Ng, Pui, White, Brian H., Casaubon, Rebecca, Narayan, Radha, Koppetsch, Karsten, Bourbonais, Francis, Wu, Bo, Wang, Junfeng, Qian, Dongming, Jiang, Fan, Mao, Cheney, Wang, Minghui, Hu, Erding, Wu, Joe C., Perni, Robert B., Vlasuk, George P., and Ellis, James L. Crystallographic structure of a small molecule SIRT1 activator-enzyme complex. United States: N. p., 2015. Web. doi:10.1038/ncomms8645.
Dai, Han, Case, April W., Riera, Thomas V., Considine, Thomas, Lee, Jessica E., Hamuro, Yoshitomo, Zhao, Huizhen, Jiang, Yong, Sweitzer, Sharon M., Pietrak, Beth, Schwartz, Benjamin, Blum, Charles A., Disch, Jeremy S., Caldwell, Richard, Szczepankiewicz, Bruce, Oalmann, Christopher, Yee Ng, Pui, White, Brian H., Casaubon, Rebecca, Narayan, Radha, Koppetsch, Karsten, Bourbonais, Francis, Wu, Bo, Wang, Junfeng, Qian, Dongming, Jiang, Fan, Mao, Cheney, Wang, Minghui, Hu, Erding, Wu, Joe C., Perni, Robert B., Vlasuk, George P., & Ellis, James L. Crystallographic structure of a small molecule SIRT1 activator-enzyme complex. United States. doi:10.1038/ncomms8645.
Dai, Han, Case, April W., Riera, Thomas V., Considine, Thomas, Lee, Jessica E., Hamuro, Yoshitomo, Zhao, Huizhen, Jiang, Yong, Sweitzer, Sharon M., Pietrak, Beth, Schwartz, Benjamin, Blum, Charles A., Disch, Jeremy S., Caldwell, Richard, Szczepankiewicz, Bruce, Oalmann, Christopher, Yee Ng, Pui, White, Brian H., Casaubon, Rebecca, Narayan, Radha, Koppetsch, Karsten, Bourbonais, Francis, Wu, Bo, Wang, Junfeng, Qian, Dongming, Jiang, Fan, Mao, Cheney, Wang, Minghui, Hu, Erding, Wu, Joe C., Perni, Robert B., Vlasuk, George P., and Ellis, James L. Thu . "Crystallographic structure of a small molecule SIRT1 activator-enzyme complex". United States. doi:10.1038/ncomms8645.
@article{osti_1497154,
title = {Crystallographic structure of a small molecule SIRT1 activator-enzyme complex},
author = {Dai, Han and Case, April W. and Riera, Thomas V. and Considine, Thomas and Lee, Jessica E. and Hamuro, Yoshitomo and Zhao, Huizhen and Jiang, Yong and Sweitzer, Sharon M. and Pietrak, Beth and Schwartz, Benjamin and Blum, Charles A. and Disch, Jeremy S. and Caldwell, Richard and Szczepankiewicz, Bruce and Oalmann, Christopher and Yee Ng, Pui and White, Brian H. and Casaubon, Rebecca and Narayan, Radha and Koppetsch, Karsten and Bourbonais, Francis and Wu, Bo and Wang, Junfeng and Qian, Dongming and Jiang, Fan and Mao, Cheney and Wang, Minghui and Hu, Erding and Wu, Joe C. and Perni, Robert B. and Vlasuk, George P. and Ellis, James L.},
abstractNote = {},
doi = {10.1038/ncomms8645},
journal = {Nature Communications},
issn = {2041-1723},
number = 1,
volume = 6,
place = {United States},
year = {2015},
month = {7}
}

Works referenced in this record:

Are sirtuins viable targets for improving healthspan and lifespan?
journal, June 2012

  • Baur, Joseph A.; Ungvari, Zoltan; Minor, Robin K.
  • Nature Reviews Drug Discovery, Vol. 11, Issue 6
  • DOI: 10.1038/nrd3738

Structural Basis for Sirtuin Activity and Inhibition
journal, October 2012


SIRT1 inhibits inflammatory pathways in macrophages and modulates insulin sensitivity
journal, March 2010

  • Yoshizaki, Takeshi; Schenk, Simon; Imamura, Takeshi
  • American Journal of Physiology-Endocrinology and Metabolism, Vol. 298, Issue 3
  • DOI: 10.1152/ajpendo.00417.2009

xia2 : an expert system for macromolecular crystallography data reduction
journal, December 2009


Crystal Structures of Human SIRT3 Displaying Substrate-induced Conformational Changes
journal, June 2009

  • Jin, Lei; Wei, Wentao; Jiang, Yaobin
  • Journal of Biological Chemistry, Vol. 284, Issue 36
  • DOI: 10.1074/jbc.M109.014928

Evidence for a Common Mechanism of SIRT1 Regulation by Allosteric Activators
journal, March 2013


Structural basis for allosteric stimulation of Sir2 activity by Sir4 binding
journal, January 2013


SIRT1 Contains N- and C-terminal Regions That Potentiate Deacetylase Activity
journal, December 2011

  • Pan, Min; Yuan, Hua; Brent, Michael
  • Journal of Biological Chemistry, Vol. 287, Issue 4
  • DOI: 10.1074/jbc.M111.285031

Phylogenetic Classification of Prokaryotic and Eukaryotic Sir2-like Proteins
journal, July 2000

  • Frye, Roy A.
  • Biochemical and Biophysical Research Communications, Vol. 273, Issue 2
  • DOI: 10.1006/bbrc.2000.3000

Coot model-building tools for molecular graphics
journal, November 2004

  • Emsley, Paul; Cowtan, Kevin
  • Acta Crystallographica Section D Biological Crystallography, Vol. 60, Issue 12, p. 2126-2132
  • DOI: 10.1107/S0907444904019158

SIRT1 Exerts Anti-Inflammatory Effects and Improves Insulin Sensitivity in Adipocytes
journal, December 2008

  • Yoshizaki, T.; Milne, J. C.; Imamura, T.
  • Molecular and Cellular Biology, Vol. 29, Issue 5
  • DOI: 10.1128/MCB.00705-08

Small molecule activators of SIRT1 as therapeutics for the treatment of type 2 diabetes
journal, November 2007

  • Milne, Jill C.; Lambert, Philip D.; Schenk, Simon
  • Nature, Vol. 450, Issue 7170
  • DOI: 10.1038/nature06261

From Sirtuin Biology to Human Diseases: An Update
journal, October 2012

  • Sebastián, Carlos; Satterstrom, F. Kyle; Haigis, Marcia C.
  • Journal of Biological Chemistry, Vol. 287, Issue 51
  • DOI: 10.1074/jbc.R112.402768

Structural basis for sirtuin function: What we know and what we don't
journal, August 2010

  • Sanders, Brandi D.; Jackson, Brittany; Marmorstein, Ronen
  • Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics, Vol. 1804, Issue 8
  • DOI: 10.1016/j.bbapap.2009.09.009

Synthesis of Carba-NAD and the Structures of Its Ternary Complexes with SIRT3 and SIRT5
journal, August 2012

  • Szczepankiewicz, Bruce G.; Dai, Han; Koppetsch, Karsten J.
  • The Journal of Organic Chemistry, Vol. 77, Issue 17
  • DOI: 10.1021/jo301067e

Sirtuin regulation of mitochondria: energy production, apoptosis, and signaling
journal, December 2010

  • Verdin, Eric; Hirschey, Matthew D.; Finley, Lydia W. S.
  • Trends in Biochemical Sciences, Vol. 35, Issue 12
  • DOI: 10.1016/j.tibs.2010.07.003

PHENIX : building new software for automated crystallographic structure determination
journal, October 2002

  • Adams, Paul D.; Grosse-Kunstleve, Ralf W.; Hung, Li-Wei
  • Acta Crystallographica Section D Biological Crystallography, Vol. 58, Issue 11
  • DOI: 10.1107/S0907444902016657

SirT1 Gain of Function Increases Energy Efficiency and Prevents Diabetes in Mice
journal, October 2008


Molecular architecture of the human protein deacetylase Sirt1 and its regulation by AROS and resveratrol
journal, May 2013

  • Lakshminarasimhan, Mahadevan; Curth, Ute; Moniot, Sebastien
  • Bioscience Reports, Vol. 33, Issue 3
  • DOI: 10.1042/BSR20120121

Discovery of Thieno[3,2- d ]pyrimidine-6-carboxamides as Potent Inhibitors of SIRT1, SIRT2, and SIRT3
journal, April 2013

  • Disch, Jeremy S.; Evindar, Ghotas; Chiu, Cynthia H.
  • Journal of Medicinal Chemistry, Vol. 56, Issue 9
  • DOI: 10.1021/jm400204k

SIRT1 Activation by Small Molecules: KINETIC AND BIOPHYSICAL EVIDENCE FOR DIRECT INTERACTION OF ENZYME AND ACTIVATOR
journal, August 2010

  • Dai, Han; Kustigian, Lauren; Carney, David
  • Journal of Biological Chemistry, Vol. 285, Issue 43
  • DOI: 10.1074/jbc.M110.133892

Discovery of Indoles as Potent and Selective Inhibitors of the Deacetylase SIRT1
journal, December 2005

  • Napper, Andrew D.; Hixon, Jeffrey; McDonagh, Thomas
  • Journal of Medicinal Chemistry, Vol. 48, Issue 25
  • DOI: 10.1021/jm050522v

Discovery of Imidazo[1,2- b ]thiazole Derivatives as Novel SIRT1 Activators
journal, March 2009

  • Vu, Chi B.; Bemis, Jean E.; Disch, Jeremy S.
  • Journal of Medicinal Chemistry, Vol. 52, Issue 5
  • DOI: 10.1021/jm8012954

Mammalian sirtuins--emerging roles in physiology, aging, and calorie restriction
journal, November 2006

  • Haigis, M. C.; Guarente, L. P.
  • Genes & Development, Vol. 20, Issue 21
  • DOI: 10.1101/gad.1467506

Structural and Functional Analysis of Human SIRT1
journal, February 2014

  • Davenport, Andrew M.; Huber, Ferdinand M.; Hoelz, André
  • Journal of Molecular Biology, Vol. 426, Issue 3
  • DOI: 10.1016/j.jmb.2013.10.009

A continuous microplate assay for sirtuins and nicotinamide-producing enzymes
journal, November 2009

  • Smith, Brian C.; Hallows, William C.; Denu, John M.
  • Analytical Biochemistry, Vol. 394, Issue 1
  • DOI: 10.1016/j.ab.2009.07.019

Recent progress in the biology and physiology of sirtuins
journal, July 2009

  • Finkel, Toren; Deng, Chu-Xia; Mostoslavsky, Raul
  • Nature, Vol. 460, Issue 7255
  • DOI: 10.1038/nature08197

Peptide Switch Is Essential for Sirt1 Deacetylase Activity
journal, October 2011


SIRT1 deacetylase protects against neurodegeneration in models for Alzheimer's disease and amyotrophic lateral sclerosis
journal, June 2007


SRT1720, SRT2183, SRT1460, and Resveratrol Are Not Direct Activators of SIRT1
journal, January 2010

  • Pacholec, Michelle; Bleasdale, John E.; Chrunyk, Boris
  • Journal of Biological Chemistry, Vol. 285, Issue 11
  • DOI: 10.1074/jbc.M109.088682

Optimizing the stability of single-chain proteins by linker length and composition mutagenesis
journal, May 1998

  • Robinson, C. R.; Sauer, R. T.
  • Proceedings of the National Academy of Sciences, Vol. 95, Issue 11
  • DOI: 10.1073/pnas.95.11.5929

Phaser crystallographic software
journal, July 2007

  • McCoy, Airlie J.; Grosse-Kunstleve, Ralf W.; Adams, Paul D.
  • Journal of Applied Crystallography, Vol. 40, Issue 4
  • DOI: 10.1107/S0021889807021206

Small molecule activators of sirtuins extend Saccharomyces cerevisiae lifespan
journal, August 2003

  • Howitz, Konrad T.; Bitterman, Kevin J.; Cohen, Haim Y.
  • Nature, Vol. 425, Issue 6954
  • DOI: 10.1038/nature01960

Mammalian Sirtuins: Biological Insights and Disease Relevance
journal, January 2010