protein hydroxylation

Definition

Target type: biologicalprocess

The addition of a hydroxy group to a protein amino acid. [GOC:ai]

Protein hydroxylation is a crucial post-translational modification process that involves the enzymatic addition of a hydroxyl group (-OH) to a specific amino acid residue within a protein. This modification plays a vital role in regulating protein structure, function, and stability, and it is implicated in a wide array of biological processes.

Hydroxylation typically occurs on proline, lysine, and asparagine residues, although other amino acids can be hydroxylated under specific circumstances. The enzymatic machinery responsible for hydroxylation comprises a diverse group of enzymes known as hydroxylases. These enzymes require molecular oxygen (O2) and a reducing agent, often NADH or NADPH, as cofactors to catalyze the hydroxylation reaction.

The specific amino acid residue targeted for hydroxylation is determined by the substrate specificity of the hydroxylase enzyme. For instance, prolyl hydroxylases (PHDs) specifically target proline residues, while lysyl hydroxylases target lysine residues.

One of the most well-studied examples of protein hydroxylation is the modification of collagen, a major component of connective tissues. Hydroxylation of proline residues in collagen is essential for the formation of stable triple helical structures that provide strength and flexibility to tissues. Deficiencies in collagen hydroxylation can lead to genetic diseases like scurvy, which is characterized by weakened connective tissues.

Another notable example of protein hydroxylation involves the regulation of hypoxia-inducible factor 1 (HIF-1). HIF-1 is a transcription factor that plays a central role in cellular responses to low oxygen levels (hypoxia). Hydroxylation of specific proline residues in HIF-1 by PHDs targets it for ubiquitination and proteasomal degradation, effectively turning off its transcriptional activity. This mechanism ensures that HIF-1 is only active under hypoxic conditions, allowing cells to adapt to low oxygen availability.

In addition to regulating protein structure and function, protein hydroxylation also plays a role in cellular signaling pathways. For example, hydroxylation of specific lysine residues in histones, the proteins that package DNA, can influence gene expression by altering chromatin structure.

In summary, protein hydroxylation is a fundamental post-translational modification that plays a crucial role in diverse biological processes. Its impact on protein structure, function, stability, and signaling pathways highlights its importance in maintaining cellular homeostasis and regulating a wide range of physiological functions.'
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Proteins (3)

Compounds (12)