Ubiquitin-activating enzyme: Difference between revisions

Revision as of 00:45, 10 February 2025

Enzyme that activates ubiquitin in the ubiquitination process

Ubiquitin-activating enzyme (E1) is a crucial enzyme in the process of ubiquitination, which is the attachment of ubiquitin to a substrate protein. This process is essential for various cellular functions, including protein degradation, cell cycle regulation, and DNA repair.

Structure

Ubiquitin-activating enzymes are characterized by their ability to bind ATP and ubiquitin. The enzyme has a catalytic cysteine residue that forms a thioester bond with ubiquitin. The structure of E1 is complex, involving multiple domains that facilitate its interaction with ATP and ubiquitin.

Mechanism

The ubiquitin-activating enzyme initiates the ubiquitination process by catalyzing the adenylation of ubiquitin, which involves the binding of ATP and ubiquitin to form a ubiquitin-adenylate intermediate. This is followed by the transfer of ubiquitin to the active site cysteine of E1, forming a thioester bond.

Function

E1 enzymes are responsible for the activation of ubiquitin, which is then transferred to a ubiquitin-conjugating enzyme (E2). This activation is the first step in the ubiquitination cascade, which ultimately leads to the attachment of ubiquitin to target proteins. This process is vital for the regulation of protein turnover and cellular homeostasis.

Active Site

The active site of the ubiquitin-activating enzyme contains a cysteine residue that is crucial for its catalytic activity. This cysteine forms a transient thioester bond with ubiquitin, facilitating its transfer to E2 enzymes.

Role in Ubiquitination

Ubiquitination is a post-translational modification that tags proteins for degradation by the proteasome. The ubiquitin-activating enzyme is the first enzyme in the ubiquitination pathway, playing a pivotal role in the regulation of protein levels within the cell.

Related pages

References

Hershko, A., & Ciechanover, A. (1998). The ubiquitin system. Annual Review of Biochemistry, 67, 425-479.
Pickart, C. M. (2001). Mechanisms underlying ubiquitination. Annual Review of Biochemistry, 70, 503-533.

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-'''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.
+{{Short description|Enzyme that activates ubiquitin in the ubiquitination process}}
+{{Use dmy dates|date=October 2023}}
-== Function ==
+'''Ubiquitin-activating enzyme''' ('''E1''') is a crucial enzyme in the process of [[ubiquitination]], which is the attachment of [[ubiquitin]] to a substrate protein. This process is essential for various cellular functions, including [[protein degradation]], [[cell cycle]] regulation, and [[DNA repair]].
-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 characterized by their ability to bind [[ATP]] and ubiquitin. The enzyme has a catalytic cysteine residue that forms a thioester bond with ubiquitin. The structure of E1 is complex, involving multiple domains that facilitate its interaction with ATP and ubiquitin.
-== Structure ==
+[[File:Ubiquitin-activating_enzyme_bound_to_Ubiquitin.png|thumb|Ubiquitin-activating enzyme bound to ubiquitin.]]
-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.
+==Mechanism==
+The ubiquitin-activating enzyme initiates the ubiquitination process by catalyzing the adenylation of ubiquitin, which involves the binding of ATP and ubiquitin to form a ubiquitin-adenylate intermediate. This is followed by the transfer of ubiquitin to the active site cysteine of E1, forming a thioester bond.
-== Clinical significance ==
+[[File:Mechanism_for_the_binding_of_ATP_and_then_Ubiquitin_substrate_to_the_ubiquitin_activating_enzyme.png|thumb|Mechanism for the binding of ATP and then ubiquitin substrate to the ubiquitin-activating enzyme.]]
-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]].
+==Function==
+E1 enzymes are responsible for the activation of ubiquitin, which is then transferred to a [[ubiquitin-conjugating enzyme]] (E2). This activation is the first step in the ubiquitination cascade, which ultimately leads to the attachment of ubiquitin to target proteins. This process is vital for the regulation of protein turnover and cellular homeostasis.
-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]].
+==Active Site==
+The active site of the ubiquitin-activating enzyme contains a cysteine residue that is crucial for its catalytic activity. This cysteine forms a transient thioester bond with ubiquitin, facilitating its transfer to E2 enzymes.
-== See also ==
+[[File:Ubiquitin_activating_enzyme_cysteine_highlighted.png|thumb|Cysteine highlighted in the active site of ubiquitin-activating enzyme.]]
+==Role in Ubiquitination==
+Ubiquitination is a post-translational modification that tags proteins for degradation by the [[proteasome]]. The ubiquitin-activating enzyme is the first enzyme in the ubiquitination pathway, playing a pivotal role in the regulation of protein levels within the cell.
+[[File:Ubiquitylation.png|thumb|Diagram of the ubiquitylation process.]]
+==Related pages==
 * [[Ubiquitin-conjugating enzyme]]
 * [[Ubiquitin ligase]]
-* [[Ubiquitin-proteasome system]]
+* [[Proteasome]]
-* [[Protein degradation]]
+==References==
+* Hershko, A., & Ciechanover, A. (1998). The ubiquitin system. Annual Review of Biochemistry, 67, 425-479.
+* Pickart, C. M. (2001). Mechanisms underlying ubiquitination. Annual Review of Biochemistry, 70, 503-533.
 [[Category:Enzymes]]
-[[Category:Protein metabolism]]
+[[Category:Ubiquitin system]]
-[[Category:Cell biology]]
-{{Enzyme-stub}}