peptidyl-lysine acetylation

Definition

Target type: biologicalprocess

The acetylation of peptidyl-lysine. [GOC:mah]

Peptidyl-lysine acetylation is a fundamental post-translational modification (PTM) that involves the covalent attachment of an acetyl group (CH3CO) to the ε-amino group of lysine residues within proteins. This modification plays a crucial role in regulating a wide range of cellular processes, including gene expression, protein stability, and signal transduction.

The enzymatic machinery responsible for peptidyl-lysine acetylation is comprised of a family of enzymes known as lysine acetyltransferases (KATs), also referred to as histone acetyltransferases (HATs) due to their initial discovery as enzymes that acetylate histones. KATs catalyze the transfer of an acetyl group from a donor molecule, typically acetyl-CoA, to the ε-amino group of lysine residues. There are distinct families of KATs:

* **N-terminal acetyltransferases (NATs):** These enzymes primarily acetylate the N-terminal residues of proteins, often the first methionine residue.

* **Histone acetyltransferases (HATs):** These enzymes specifically acetylate lysine residues within histone proteins, which are major components of chromatin. Histone acetylation is crucial for regulating gene expression by altering chromatin structure and accessibility to transcription factors.

* **Non-histone acetyltransferases (NHATs):** These enzymes target a diverse range of non-histone proteins, including transcription factors, signaling molecules, and metabolic enzymes. Acetylation of these proteins can modulate their activity, stability, or interactions with other proteins.

**The biological process of peptidyl-lysine acetylation involves the following steps:**

1. **Substrate recognition:** KATs recognize specific lysine residues within their target proteins. The surrounding amino acid sequence, the protein's structure, and the cellular context can influence substrate selectivity.

2. **Acetyl-CoA binding:** KATs bind to acetyl-CoA, the donor molecule that provides the acetyl group for the modification.

3. **Lysine deprotonation:** The ε-amino group of the lysine residue undergoes deprotonation, making it more susceptible to acetylation.

4. **Acetyl group transfer:** The acetyl group from acetyl-CoA is transferred to the ε-amino group of the lysine residue, forming an acetyl-lysine moiety.

5. **Product release:** After acetylation, the modified protein is released from the KAT enzyme.

**The biological consequences of peptidyl-lysine acetylation are multifaceted and include:**

* **Gene expression regulation:** Acetylation of histone proteins alters chromatin structure, making genes more or less accessible to transcription factors. This can lead to increased or decreased gene expression, respectively.

* **Protein stability:** Acetylation can influence the stability of proteins by affecting their susceptibility to degradation.

* **Protein-protein interactions:** Acetylation can modify the interaction of proteins with other molecules, including DNA, RNA, and other proteins. This can impact protein function and signaling pathways.

* **Cellular signaling:** Acetylation is involved in various signaling pathways, including those that control cell growth, differentiation, and metabolism.

* **Metabolic regulation:** Acetylation plays a role in regulating metabolic processes, including glucose metabolism and fatty acid synthesis.

Overall, peptidyl-lysine acetylation is a highly dynamic and intricate process that regulates a wide spectrum of cellular functions. Dysregulation of this modification can contribute to various diseases, including cancer, neurodegenerative disorders, and metabolic diseases.'
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Proteins (4)

Compounds (61)