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Introduction of Bifunctionality into the Multidomain Architecture of the ω-Ester-Containing Peptide Plesiocin.
- Source :
-
Biochemistry [Biochemistry] 2020 Jan 28; Vol. 59 (3), pp. 285-289. Date of Electronic Publication: 2019 Oct 28. - Publication Year :
- 2020
-
Abstract
- The modular biosynthetic pathway of ribosomally synthesized and post-translationally modified peptides (RiPPs) enhances their engineering potential for exploring new structures and biological functions. The ω-ester-containing peptides (OEPs), a subfamily of RiPPs, have distinct side-to-side ester or amide linkages and frequently present more than one macrocyclic domain in a "beads-on-a-string" structure. In an effort to improve the engineering potential of RiPPs, we present here the idea that the multidomain architecture of an OEP, plesiocin, can be exploited to create a bifunctional modified peptide. Characterization of plesiocin variants revealed that strong chymotrypsin inhibition relies on the bicyclic structure of the domain in which a leucine residue in the hairpin loop functions as a specificity determinant. Four domains of plesiocin promote simultaneous binding of multiple enzymes, where the C-terminal domain binds chymotrypsin most efficiently. Using this information, we successfully engineered a plesiocin variant in which two different domains inhibit chymotrypsin and trypsin. This result suggests that the multidomain architecture of OEPs is a useful platform for engineering multifunctional hybrid RiPPs.
- Subjects :
- Biosynthetic Pathways drug effects
Chromatography, High Pressure Liquid
Chymotrypsin chemistry
Cloning, Molecular
Escherichia coli genetics
Esters chemistry
Peptides genetics
Peptides isolation & purification
Protease Inhibitors chemistry
Protease Inhibitors pharmacology
Protein Binding genetics
Protein Domains genetics
Protein Processing, Post-Translational genetics
Ribosomes chemistry
Ribosomes genetics
Trypsin chemistry
Trypsin genetics
Trypsin Inhibitors chemistry
Chymotrypsin antagonists & inhibitors
Peptides chemistry
Protein Engineering
Subjects
Details
- Language :
- English
- ISSN :
- 1520-4995
- Volume :
- 59
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Biochemistry
- Publication Type :
- Academic Journal
- Accession number :
- 31644266
- Full Text :
- https://doi.org/10.1021/acs.biochem.9b00803