metallopeptidase activity

Definition

Target type: molecularfunction

Catalysis of the hydrolysis of peptide bonds by a mechanism in which water acts as a nucleophile, one or two metal ions hold the water molecule in place, and charged amino acid side chains are ligands for the metal ions. [GOC:mah, https://www.ebi.ac.uk/merops/about/glossary.shtml#CATTYPE]

Metallopeptidase activity refers to the catalytic ability of enzymes to cleave peptide bonds in proteins or peptides, utilizing a metal ion as a cofactor in the active site. The metal ion plays a crucial role in facilitating the reaction, often acting as a Lewis acid to activate the water molecule required for hydrolysis or stabilizing the transition state.

The mechanism of metallopeptidase activity involves the following steps:

1. **Substrate Binding:** The enzyme binds the substrate, typically a peptide or protein, to its active site. The metal ion in the active site interacts with the substrate, often through coordination bonds, to position it correctly for cleavage.

2. **Metal Ion Activation:** The metal ion, typically a zinc ion, activates a water molecule by polarizing its oxygen atom. This increases the nucleophilicity of the water molecule, making it a more effective nucleophile.

3. **Nucleophilic Attack:** The activated water molecule attacks the carbonyl carbon of the peptide bond, forming a tetrahedral intermediate. This step is facilitated by the metal ion, which stabilizes the negatively charged oxygen atom in the tetrahedral intermediate.

4. **Bond Cleavage:** The tetrahedral intermediate collapses, breaking the peptide bond and releasing the carboxyl group of the cleaved peptide.

5. **Product Release:** The cleaved peptide products are released from the active site, allowing the enzyme to bind another substrate and repeat the catalytic cycle.

Metallopeptidases are broadly classified based on their active site structure and metal ion cofactor:

* **Zinc Metallopeptidases:** Utilize zinc ions as the catalytic metal. Examples include carboxypeptidases, thermolysin, and matrix metalloproteinases (MMPs).
* **Manganese Metallopeptidases:** Utilize manganese ions as the catalytic metal. Examples include arginase and superoxide dismutase.
* **Other Metallopeptidases:** Utilize metal ions such as cobalt, nickel, or iron in their active sites.

Metallopeptidases play essential roles in various cellular processes, including protein turnover, signal transduction, and regulation of cellular growth and development. They are also involved in various disease processes, such as cancer, Alzheimer's disease, and cardiovascular disease. The diverse functions and therapeutic potential of metallopeptidases have made them an active area of research.'
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Proteins (19)

Compounds (817)