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Structure-Based Engineering of Peptide Macrocyclases for the Chemoenzymatic Synthesis of Microviridins.
- Source :
-
The Journal of organic chemistry [J Org Chem] 2021 Aug 20; Vol. 86 (16), pp. 11212-11219. Date of Electronic Publication: 2021 Jul 15. - Publication Year :
- 2021
-
Abstract
- Microviridins are cyanobacterial tricyclic depsipeptides with unique ring architectures and function as serine protease inhibitors. In this study, we explore two strategies to probe the structure and mechanism of macrocyclases involved in microviridin biosynthesis. The results both provide approaches for in vitro chemoenzymatic synthesis and insight into the molecular interactions and function of the biosynthetic enzymes. The first strategy involves generating constitutively activated macrocyclases whereby the leader portion of the substrate peptide is covalently attached to the ATP-grasp ligases to examine leader peptide/enzyme interactions. The second strategy uses a structure-based design to create disulfide cross-linked peptide/enzyme complexes. Together, the strategies provide constitutively active enzymes and tools to study the catalysis of the macrocyclizations on synthetic core peptides.
- Subjects :
- Ligases
Serine Proteinase Inhibitors
Cyanobacteria
Peptides
Subjects
Details
- Language :
- English
- ISSN :
- 1520-6904
- Volume :
- 86
- Issue :
- 16
- Database :
- MEDLINE
- Journal :
- The Journal of organic chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 34263606
- Full Text :
- https://doi.org/10.1021/acs.joc.1c00785