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The Acyl-CoA Specificity of Human Lysine Acetyltransferase KAT2A.

ABSTRACT: Protein post-translational modifications serve to regulate a broad range of cellular functions including signal transduction, transcription, and metabolism. Protein lysine residues undergo many post-translational acylations and are regulated by a range of enzymes, such as histone acetyl transferases (HATs) and histone deacetylases (HDACs). KAT2A, well characterized as a lysine acetyltransferase for both histone and nonhistone substrates, has been reported to tolerate additional acyl-CoA substrates, such as succinyl-CoA, and shows nonacetyl transferase activity in specific biological contexts. In this work, we investigate the acyl-CoA substrate preference of KAT2A and attempt to determine whether and to what extent additional acyl-CoA substrates may be utilized by KAT2A in a cellular context. We show that while KAT2A can bind and utilize malonyl-CoA, its activity with succinyl-CoA or glutaryl-CoA is very weak, and acetylation is still the most efficient activity for KAT2A in vitro and in cells.

SUBMITTER: Anmangandla A

PROVIDER: S-EPMC9454090 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature

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The Acyl-CoA Specificity of Human Lysine Acetyltransferase KAT2A.

Anmangandla Ananya A Ren Yuxiang Y Fu Qin Q Zhang Sheng S Lin Hening H

Biochemistry 20220822 17

Protein post-translational modifications serve to regulate a broad range of cellular functions including signal transduction, transcription, and metabolism. Protein lysine residues undergo many post-translational acylations and are regulated by a range of enzymes, such as histone acetyl transferases (HATs) and histone deacetylases (HDACs). KAT2A, well characterized as a lysine acetyltransferase for both histone and nonhistone substrates, has been reported to tolerate additional acyl-CoA substrat ...[more]

PMID: 35995428

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