Ubiquitin-activating enzyme

Ubiquitin-activating enzyme (also known as E1 enzyme) is the first enzyme in the ubiquitin-proteasome system, a biological pathway involved in protein degradation. This enzyme plays a crucial role in the protein degradation process, which is essential for maintaining cellular homeostasis.

Function

The ubiquitin-activating enzyme catalyzes the first step in the ubiquitin-proteasome system. It activates ubiquitin by forming a high-energy thioester bond between the C-terminal glycine residue of ubiquitin and its own cysteine residue. This process requires ATP. The activated ubiquitin is then transferred to a ubiquitin-conjugating enzyme (E2), and finally to a ubiquitin ligase (E3), which attaches the ubiquitin to a target protein.

Structure

Ubiquitin-activating enzymes are large proteins, typically composed of more than 1000 amino acids. They have a modular structure, with several domains that are responsible for binding to ubiquitin, ATP, and the E2 enzyme. The active site, where the thioester bond is formed, is located in a cleft between two domains.

Clinical significance

Mutations in the genes encoding ubiquitin-activating enzymes can lead to various diseases. For example, mutations in the UBA1 gene, which encodes a ubiquitin-activating enzyme, have been associated with X-linked spinal muscular atrophy.

In addition, ubiquitin-activating enzymes are potential targets for drug development. Inhibitors of these enzymes could be used to treat diseases that are caused by excessive protein degradation, such as cancer and neurodegenerative diseases.

See also

• Ubiquitin-conjugating enzyme
• Ubiquitin ligase
• Ubiquitin-proteasome system
• Protein degradation

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