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org/10.1074/jbc.M109.014928
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0 -bromo-resveratrol reveal binding sites and inhibition mechanism. Chem Biol 20
(11):1375–1385. https://doi.org/10.1016/j.chembiol.2013.09.019
73. Nguyen GTT, Schaefer S, Gertz M, Weyand M, Steegborn C (2013) Structures of human
sirtuin 3 complexes with ADP-ribose and with carba-NAD(+) and SRT1720: binding details
and inhibition mechanism. Acta Crystallogr D 69:1423–1432. https://doi.org/10.1107/
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74. Szczepankiewicz BG, Dai H, Koppetsch KJ, Qian DM, Jiang F, Mao C, Perni RB (2012)
Synthesis of carba-NAD and the structures of its ternary complexes with SIRT3 and SIRT5.
J Org Chem 77(17):7319–7329. https://doi.org/10.1021/jo301067e
75. Wu JH, Zhang DY, Chen L, Li JN, Wang JL, Ning CQ, Yu NF, Zhao F, Chen DY, Chen XY,
Chen KX, Jiang HL, Liu H, Liu DX (2013) Discovery and mechanism study of SIRT1
activators that promote the deacetylation of fluorophore-labeled substrate. J Med Chem 56
(3):761–780. https://doi.org/10.1021/jm301032j
76. Du JT, Zhou YY, Su XY, Yu JJ, Khan S, Jiang H, Kim J, Woo J, Kim JH, Choi BH, He B,
Chen W, Zhang S, Cerione RA, Auwerx J, Hao Q, Lin HN (2011) Sirt5 is a NAD-dependent
protein lysine demalonylase and desuccinylase. Science 334(6057):806–809. https://doi.org/
10.1126/science.1207861
77. Schuetz A, Min JR, Antoshenko T, Wang CL, Allali-Hassani A, Dong AP, Loppnau P,
Vedadi M, Bochkarev A, Sternglanz R, Plotnikov AN (2007) Structural basis of inhibition
of the human NAD(+)-dependent deacetylase SIRT5 by suramin. Structure 15(3):377–389.
https://doi.org/10.1016/j.str.2007.02.002
78. Zhou YY, Zhang HM, He B, Du JT, Lin HN, Cerione RA, Hao Q (2012) The bicyclic
intermediate structure provides insights into the desuccinylation mechanism of human sirtuin
5 (SIRT5). J Biol Chem 287(34):28307–28314. https://doi.org/10.1074/jbc.M112.384511
480
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to obtain crystals of human Sirt3 and Sirt2 suitable for soaking. Acta Crystallogr F Struct Biol
Commun 71:1498–1510. https://doi.org/10.1107/S2053230x15019986
66. Yamagata K, Goto Y, Nishimasu H, Morimoto J, Ishitani R, Dohmae N, Takeda N, Nagai R,
Komuro I, Suga H, Nureki O (2014) Structural basis for potent inhibition of SIRT2 deacetylase
by a macrocyclic peptide inducing dynamic structural change. Structure 22(2):345–352.
https://doi.org/10.1016/j.str.2013.12.001
67. Bao XC, Wang Y, Li X, Li XM, Liu Z, Yang TP, Wong CF, Zhang JW, Hao Q, Li XD (2014)
Identification of ‘erasers’ for lysine crotonylated histone marks using a chemical proteomics
approach. Elife 3. https://doi.org/10.7554/eLife.02999
68. Disch JS, Evindar G, Chiu CH, Blum CA, Dai H, Jin L, Schuman E, Lind KE, Belyanskaya
SL, Deng J, Coppo F, Aquilani L, Graybill TL, Cuozzo JW, Lavu S, Mao C, Vlasuk GP, Perni
RB (2013) Discovery of thieno[3,2-d]pyrimidine-6-carboxamides as potent inhibitors of
SIRT1, SIRT2, and SIRT3. J Med Chem 56(9):3666–3679. https://doi.org/10.1021/
jm400204k
69. Gertz M, Fischer F, Nguyen GTT, Lakshminarasimhan M, Schutkowski M, Weyand M,
Steegborn C (2013) Ex-527 inhibits sirtuins by exploiting their unique NAD(+)-dependent
deacetylation mechanism. Proc Natl Acad Sci U S A 110(30):E2772–E2781. https://doi.org/
10.1073/pnas.1303628110
70. Gertz M, Giang TTN, Fischer F, Suenkel B, Schlicker C, Franzel B, Tomaschewski J,
Aladini F, Becker C, Wolters D, Steegborn C (2012) A molecular mechanism for direct sirtuin
activation by resveratrol. Plos One 7(11):e49761. https://doi.org/10.1371/journal.pone.
0049761
71. Jin L, Wei WT, Jiang YB, Peng H, Cai JH, Mao C, Dai H, Choy W, Bemis JE, Jirousek MR,
Milne JC, Westphal CH, Perni RB (2009) Crystal structures of human SIRT3 displaying
substrate-induced conformational changes. J Biol Chem 284(36):24394–24405. https://doi.
org/10.1074/jbc.M109.014928
72. Nguyen GTT, Gertz M, Steegborn C (2013) Crystal structures of Sirt3 complexes with
4
0 -bromo-resveratrol reveal binding sites and inhibition mechanism. Chem Biol 20
(11):1375–1385. https://doi.org/10.1016/j.chembiol.2013.09.019
73. Nguyen GTT, Schaefer S, Gertz M, Weyand M, Steegborn C (2013) Structures of human
sirtuin 3 complexes with ADP-ribose and with carba-NAD(+) and SRT1720: binding details
and inhibition mechanism. Acta Crystallogr D 69:1423–1432. https://doi.org/10.1107/
S0907444913015448
74. Szczepankiewicz BG, Dai H, Koppetsch KJ, Qian DM, Jiang F, Mao C, Perni RB (2012)
Synthesis of carba-NAD and the structures of its ternary complexes with SIRT3 and SIRT5.
J Org Chem 77(17):7319–7329. https://doi.org/10.1021/jo301067e
75. Wu JH, Zhang DY, Chen L, Li JN, Wang JL, Ning CQ, Yu NF, Zhao F, Chen DY, Chen XY,
Chen KX, Jiang HL, Liu H, Liu DX (2013) Discovery and mechanism study of SIRT1
activators that promote the deacetylation of fluorophore-labeled substrate. J Med Chem 56
(3):761–780. https://doi.org/10.1021/jm301032j
76. Du JT, Zhou YY, Su XY, Yu JJ, Khan S, Jiang H, Kim J, Woo J, Kim JH, Choi BH, He B,
Chen W, Zhang S, Cerione RA, Auwerx J, Hao Q, Lin HN (2011) Sirt5 is a NAD-dependent
protein lysine demalonylase and desuccinylase. Science 334(6057):806–809. https://doi.org/
10.1126/science.1207861
77. Schuetz A, Min JR, Antoshenko T, Wang CL, Allali-Hassani A, Dong AP, Loppnau P,
Vedadi M, Bochkarev A, Sternglanz R, Plotnikov AN (2007) Structural basis of inhibition
of the human NAD(+)-dependent deacetylase SIRT5 by suramin. Structure 15(3):377–389.
https://doi.org/10.1016/j.str.2007.02.002
78. Zhou YY, Zhang HM, He B, Du JT, Lin HN, Cerione RA, Hao Q (2012) The bicyclic
intermediate structure provides insights into the desuccinylation mechanism of human sirtuin
5 (SIRT5). J Biol Chem 287(34):28307–28314. https://doi.org/10.1074/jbc.M112.384511
480
D. Robaa et al.