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Reply to: Binding site for MDL-801 on SIRT6

Nature Chemical Biology volume 17, pages 522–523 (2021)Cite this article

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The Original Article was published on 01 March 2021

replying to W. You and C. Steegborn Nature Chemical Biology https://doi.org/10.1038/s41589-021-00749-y (2021)

You and Steegborn1, in their correspondence related to our recent article about the identification of SIRT6 allosteric activators, have raised concerns that the observed electron density for activator MDL-801 in our structure for myristoylated substrate-bound SIRT6–MDL-801 complex2 may have been associated with a crystallization buffer molecule, morpholinoethanesulfonic acid (MES). In addition, they separately determined crystal structures for SIRT6–MDL-801 complexes lacking the SIRT6 substrate showing that MDL-801 binds in a manner perpendicular to our binding mode at the same site.

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Fig. 1: MDL-801 at the SIRT6 site.

Data availability

The crystal structures of apo SIRT6 and SIRT6 in complex with MDL-801 have been deposited in the PDB under accession codes 7CL0 and 7CL1, respectively.

References

  1. You, W. & Steegborn, C. Binding site for MDL-801 on SIRT6. Nat. Chem. Biol. https://doi.org/10.1038/s41589-021-00749-y (2021).

  2. Huang, Z. et al. Identification of a cellularly active SIRT6 allosteric activator. Nat. Chem. Biol. 14, 1118–1126 (2018).

    Article  CAS  Google Scholar 

  3. Jiang, H. et al. SIRT6 regulates TNF-α secretion through hydrolysis of long-chain fatty acyl lysine. Nature 496, 110–113 (2013).

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Pathophysiology, Shanghai Jiaotong University School of Medicine, Shanghai, China

    Zhimin Huang, Junxing Zhao, Wei Deng, Yingyi Chen, Jialin Shang, Kun Song, Lu Zhang, Chengxiang Wang, Shaoyong Lu, Xiuyan Yang, Jianrong Xu, Qiufen Zhang, Jie Zhong, Houwen Lin, Ying Xu, Guoqiang Chen & Jian Zhang

  2. Engineering Research Center for the Development and Application of Ethnic Medicine and TCM, Ministry of Education, Guizhou Medical University, Guiyang, China

    Bin He

  3. Structural Genomics Consortium, University of Toronto, Toronto, Ontario, Canada

    Jinrong Min

  4. Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China

    Hao Hu, Minjia Tan & Hualiang Jiang

  5. School of Life Sciences and Technology, Tongji University, Shanghai, China

    Xiaoxiang Sun & Zhiyong Mao

  6. Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China

    Mingzhe Xiao & Y. Eugene Chin

  7. Ailewei Company, Shanghai, China

    Honghua Shen

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  1. Zhimin Huang
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Contributions

Z.H., J.S. and K.S. performed the biological experiments and the crystallography. K.S. solved the crystal structures and analyzed the data. J. Zhang, S.L. and H.S. discussed the manuscript, J. Zhang and S.L. wrote the manuscript and J. Zhao, W.D., Y.C., L.Z., C.W., X.Y., B.H., J.M., H.H., M.T., J.X., Q.Z., J. Zhong, X.S., Z.M., H.L., M.X., Y.E.C., H.J., Y.X. and G.C. are the authors of our previous paper2.

Corresponding author

Correspondence to Jian Zhang.

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Competing interests

The group of J. Zhang has a collaboration with Shanghai Ailewei on SIRT6.

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Huang, Z., Zhao, J., Deng, W. et al. Reply to: Binding site for MDL-801 on SIRT6. Nat Chem Biol 17, 522–523 (2021). https://doi.org/10.1038/s41589-021-00750-5

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