Peptide Microarrays for Profiling of Epigenetic Targets

Masch, Antonia; Reimer, Ulf; Zerweck, Johannes; Schutkowski, Mike

doi:10.1016/b978-0-12-801080-8.00009-0

Cited by 2 publications

(2 citation statements)

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“…Serine phosphorylation of the H3K9 histone peptide has a pronounced effect on the K M value for the sirtuin 2 enzymatic activity, resulting in a >200-fold decrease in specificity constant. 36 Interestingly, we have not found any studies describing the effect of phosphorylation on HDAC I, II, and IV class activity, and prompted by the slight preferences of glutamic acid, phosphoserine mimetics, at +2 position over serine, we hypothesized that the phosphorylation can influence the deacetylation by class IIa HDACs. We have synthesized single peptides bearing phosphoserine, glutamate, and serine in +2 position and tested their cleavage by class IIa HDACs.…”

Section: Discussionmentioning

confidence: 99%

“…The effect of phosphorylation on deacetylation kinetics was also confirmed in the case of sirtuins (class III HDACs). Serine phosphorylation of the H3K9 histone peptide has a pronounced effect on the K M value for the sirtuin 2 enzymatic activity, resulting in a >200‐fold decrease in specificity constant 36 . Interestingly, we have not found any studies describing the effect of phosphorylation on HDAC I, II, and IV class activity, and prompted by the slight preferences of glutamic acid, phosphoserine mimetics, at +2 position over serine, we hypothesized that the phosphorylation can influence the deacetylation by class IIa HDACs.…”

Section: Discussionmentioning

confidence: 99%

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Characterization of the class IIa histone deacetylases substrate specificity

et al. 2022

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Class IIa histone deacetylases (HDACs) play critical roles in vertebrate development and physiology, yet direct evidence of their intrinsic deacetylase activity and on substrate specificity regarding the peptide sequence is still missing. In this study, we designed and synthesized a combinatorial peptide library allowing us to profile class IIa HDACs sequence specificity at positions +3 through −3 from the central lysine modified by the well‐accepted trifluoroacetyl function. Our data revealed a strong preference for bulky aromatic acids directly flanking the central trifluoroacetyllysine, while all class IIa HDACs disfavor positively charged residues and proline at the +1/‐1 positions. The chemical nature of amino acid residues N‐terminally to the central trifluoroacetyllysine has a more profound effect on substrate recognition as compared to residues located C‐terminally. These findings were validated by designing selected favored and disfavored peptide sequences, with the favored ones are accepted with catalytic efficacy of 75 000 and 525 000 M−1 s−1 for HDAC7 and HDAC5, respectively. Results reported here could help in developing class IIa HDACs inhibitors and also in the search for new natural class IIa HDACs substrates.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%