TY  - JOUR
A1  - Weiz, Annika R.
A1  - Ishida, Keishi
A1  - Quitterer, Felix
A1  - Meyer, Sabine
A1  - Kehr, Jan-Christoph
A1  - Mueller, Kristian M.
A1  - Groll, Michael
A1  - Hertweck, Christian
A1  - Dittmann-Thünemann, Elke
T1  - Harnessing the evolvability of tricyclic microviridins to dissect protease-inhibitor interactions
JF  - Angewandte Chemie : a journal of the Gesellschaft Deutscher Chemiker ; International edition
N2  - 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.
KW  - cyanobacteria
KW  - peptide engineering
KW  - protease inhibitors
KW  - RiPPs
KW  - structure elucidation
Y1  - 2014
U6  - https://doi.org/10.1002/anie.201309721
SN  - 1433-7851
SN  - 1521-3773
VL  - 53
IS  - 14
SP  - 3735
EP  - 3738
PB  - Wiley-VCH
CY  - Weinheim
ER  -