Substrate specificity of SIRT1-catalyzed lysine Nepsilon-deacetylation reaction probed with the side chain modified Nepsilon-acetyl-lysine analogs.
Peptides containing L-N(epsilon)-acetyl-lysine (L-AcK) or its side chain modified analogs were prepared and assayed using SIRT1, the prototypical human silent information regulator 2 (Sir2) enzyme. While previous studies showed that the side chain acetyl group of L-AcK can be extended to bulkier acyl groups for Sir2 (including SIRT1)-catalyzed lysine N(epsilon)-deacylation reaction, our current study suggested that SIRT1-catalyzed deacetylation reaction had a very stringent requirement for the distance between the alpha-carbon and the side chain acetamido group, with that found in L-AcK being optimal. Moreover, our current study showed that SIRT1 catalyzed the stereospecific deacetylation of L-AcK versus its D-isomer. The results from our current study shall constitute another piece of important information to be considered when designing inhibitors for SIRT1 and Sir2 enzymes in general.
Jamonnak
Nuttara
N
Department of Chemistry, University of Akron, 190 E. Buchtel Commons, Akron, OH 44325, USA.
Hirsch
Brett M
BM
Pang
Yi
Y
Zheng
Weiping
W
D055162:Biocatalysis; D006801:Humans; D008239:Lysine / Q000031:analogs & derivatives* / Q000737:chemistry; D011994:Recombinant Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D056564:Sirtuin 1 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D013237:Stereoisomerism; D013379:Substrate Specificity
D011994:Recombinant Proteins; C447939:SIRT1 protein, human; D056564:Sirtuin 1; D008239:Lysine