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Published on: April 12, 2019
Circular micro-proteins and mechanisms of cyclization
Brendon F Conlan1, Marilyn A Anderson
1Department of Biochemistry, La Trobe University, Melbourne, Victoria 3086, Australia.
Current Pharmaceutical Design
|December 30, 2011
Summary
This review explores cyclic proteins, focusing on their formation via transpeptidation reactions catalyzed by proteases. Understanding these mechanisms reveals how cyclic proteins achieve exceptional stability.
Area of Science:
- Biochemistry
- Molecular Biology
- Proteomics
Background:
- Transpeptidation reactions form new peptide bonds, leading to cyclic proteins when a single peptide's termini join.
- Cyclic proteins, though rare, exhibit remarkable stability due to their head-to-tail linkage.
- The precise mechanisms of protein cyclization remain incompletely understood.
Purpose of the Study:
- To review current knowledge on the mechanisms of protein cyclization.
- To document the enzymes involved in catalyzing transpeptidation reactions leading to cyclization.
- To highlight the diversity of cyclic proteins across different species.
Main Methods:
- Literature review of studies on transpeptidation and protein cyclization.
- Analysis of enzyme classes (cysteine, serine, threonine proteases) involved in these reactions.
- Examination of specific examples like cyclotides from Oldenlandia affinis.
Main Results:
- Cyclic proteins are found in prokaryotes (bacteriocins, pilins) and eukaryotes (θ-defensins, retrocyclins, fungal proteins, cyanobacterial proteins).
- Plants express diverse cyclic proteins, including small peptides, sunflower proteins, and cyclotides (28-37 amino acids).
- Cysteine and serine proteases catalyze cyclization, often involving an acyl enzyme intermediate and nucleophilic attack to form the cyclic peptide bond.
Conclusions:
- Protein cyclization, particularly head-to-tail linkage, confers exceptional stability.
- Asparaginyl endopeptidases (cysteine proteases) are key in processing plant cyclotides.
- Further research is needed to fully elucidate the diverse mechanisms of cyclic protein formation.
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