Harnessing the evolvability of tricyclic microviridins to dissect protease-inhibitor interactions
- Understanding and controlling proteolysis is an important goal in therapeutic chemistry. Among the natural products specifically inhibiting proteases microviridins are particularly noteworthy. Microviridins are ribosomally produced and posttranslationally modified peptides that are processed into a unique, cagelike architecture. Here, we report a combined rational and random mutagenesis approach that provides fundamental insights into selectivity-conferring moieties of microviridins. The potent variant microviridin J was co-crystallized with trypsin, and for the first time the three-dimensional structure of microviridins was determined and the mode of inhibition revealed.
Author details: | Annika R. Weiz, Keishi Ishida, Felix Quitterer, Sabine Meyer, Jan-Christoph KehrGND, Kristian M. Mueller, Michael Groll, Christian Hertweck, Elke Dittmann-ThünemannORCiDGND |
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DOI: | https://doi.org/10.1002/anie.201309721 |
ISSN: | 1433-7851 |
ISSN: | 1521-3773 |
Pubmed ID: | https://pubmed.ncbi.nlm.nih.gov/24591244 |
Title of parent work (English): | Angewandte Chemie : a journal of the Gesellschaft Deutscher Chemiker ; International edition |
Publisher: | Wiley-VCH |
Place of publishing: | Weinheim |
Publication type: | Article |
Language: | English |
Year of first publication: | 2014 |
Publication year: | 2014 |
Release date: | 2017/03/27 |
Tag: | RiPPs; cyanobacteria; peptide engineering; protease inhibitors; structure elucidation |
Volume: | 53 |
Issue: | 14 |
Number of pages: | 4 |
First page: | 3735 |
Last Page: | 3738 |
Funding institution: | German Research foundation (DFG) [Di910/4-1, He3469/4-1]; grant in the cluster of excellence UniCAT |
Organizational units: | Mathematisch-Naturwissenschaftliche Fakultät / Institut für Biochemie und Biologie |
Peer review: | Referiert |