Isopeptidase Explained

An isopeptidase is a protease enzyme that hydrolyzes isopeptide bonds, or amide bonds that occur outside the main chain in a polypeptide chain.

In protein degradation

Isopeptide bonds occur in the linkage of protein amino acid side chains to proteins such as ubiquitin and SUMO in the protein degradation pathway. In eukaryotes, enzymes with isopeptidase activity are often involved in this pathway; all five classes of deubiquitinating enzymes have isopeptidase activity.^[1] Examples include Ulp1 peptidase^[2] and USP5 (formerly known as isopeptidase T).^{[3] [4]}

In lasso peptide processing

Isopeptidases have also been identified in prokaryotes that express lasso peptides, or peptides with a knotted conformation established by the presence of a non-main-chain linkage between an acidic amino acid and the peptide's N-terminus to form the knot. (Some lasso peptides also have topological complexity conferred by disulfide bonds.) Isopeptidase enzymes linearize the peptides by cleaving the isopeptide bond.^{[5] [6]}

Notes and References

1. Sahtoe. Danny D.. Sixma. Titia K.. Layers of DUB regulation. Trends in Biochemical Sciences. August 2015. 40. 8. 456–467. 10.1016/j.tibs.2015.05.002. 26073511 .
2. Li. Shyr-Jiann. Hochstrasser. Mark. The Ulp1 SUMO isopeptidase. The Journal of Cell Biology. 31 March 2003. 160. 7. 1069–1082. 10.1083/jcb.200212052. 2172760. 12654900.
3. Wilkinson. KD. Tashayev. VL. O'Connor. LB. Larsen. CN. Kasperek. E. Pickart. CM. Metabolism of the polyubiquitin degradation signal: structure, mechanism, and role of isopeptidase T.. Biochemistry. 7 November 1995. 34. 44. 14535–46. 7578059. 10.1021/bi00044a032.
4. Clague. Michael J.. Heride. Claire. Urbé. Sylvie. The demographics of the ubiquitin system. Trends in Cell Biology. July 2015. 25. 7. 417–426. 10.1016/j.tcb.2015.03.002. 25906909 .
5. Maksimov. Mikhail O.. Link. A. James. Discovery and Characterization of an Isopeptidase That Linearizes Lasso Peptides. Journal of the American Chemical Society. 14 August 2013. 135. 32. 12038–12047. 10.1021/ja4054256. 23862624 .
6. Hegemann. Julian D.. Zimmermann. Marcel. Xie. Xiulan. Marahiel. Mohamed A.. Lasso Peptides: An Intriguing Class of Bacterial Natural Products. Accounts of Chemical Research. 21 July 2015. 48. 7. 1909–1919. 10.1021/acs.accounts.5b00156. 26079760.