Threonine protease
| Threonine Protease | |
|---|---|
| File:Protein PSMA1 PDB 1iru.png
Crystal structure of human proteasome alpha 1
|
|
| Identifiers | |
| Symbol | Thr |
Threnonine proteases are a family of proteolytic enzymes harbouring a threonine (Thr) residue within the active site. The prototype members of this class of enzymes are the catalytic subunits of the proteasome, however the acyltransferases convergently evolved the same active site geometry and mechanism.
Mechanism
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Threonine proteases use the secondary alcohol of their N-terminal threonine as a nucleophile to perform catalysis.[1][2] The threonine must be N-terminal since the terminal amide of the same residue acts as a general base by polarising an ordered water which deprotonates the alcohol to increase its reactivity as a nucleophile.[3][4]
Catalysis takes place in two steps:
- Firstly the nucleophile attacks the substrate to form a covalent acyl-enzyme intermediate, releasing the first product.
- Secondly the immediate is hydrolised by water to regenerate the free enzyme and release the second product.
- In ornithine acyltransferase, instead of water, the substrate ornithine (the acceptor) performs the second nucleophilic attack and so leaves with the acyl group.
Classification and evolution
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Five families belonging to two separate superfamilies are currently recognised: the Ntn fold proteosomes[1] (superfamily PB) and the DOM fold ornithine acyltransferases[2] (superfamily PE). The two superfamilies represent two independent, convergent evolutions of the same active site.[4][5]
| Superfamily | Threonine protease families | Examples |
|---|---|---|
| PB clan | T1, T2, T3, T6 | archaean proteasome, beta component (Thermoplasma acidophilum) |
| PE clan | T5 | ornithine acetyltransferase (Saccharomyces cerevisiae) |
See also
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- Protease
- Enzyme
- Proteolysis
- Catalytic triad
- Convergent evolution
- The Proteolysis Map
- Protease inhibitor (pharmacology)
- Protease inhibitor (biology)
- TopFIND - database of protease specificity, substrates, products and inhibitors
- MEROPS - database of protease evolutionary groups
References
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- ↑ 2.0 2.1 Lua error in package.lua at line 80: module 'strict' not found.
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