8UTL

Bovine trypsin in complex with Thr3Dap mutated microviridin J

Summary for 8UTL

• Entry DOI: 10.2210/pdb8utl/pdb
• Related: 8UO7
• Descriptor: Cationic trypsin, Thr3Dap mutated microviridin J, GLYCEROL, ... (6 entities in total)
• Functional Keywords: hydrolase inhibitor, hydrolase
• Biological source: Bos taurus (cattle); More
• Total number of polymer chains: 2
• Total formula weight: 25424.50

Authors

Chen, W.,Bruner, S.D. (deposition date: 2023-10-31, release date: 2024-02-14, Last modification date: 2024-02-28)

Primary citation

Patel, K.P.,Chen, W.T.,Delbecq, L.,Bruner, S.D.
Alternative Linkage Chemistries in the Chemoenzymatic Synthesis of Microviridin-Based Cyclic Peptides.
Org.Lett., 26:1138-1142, 2024

PubMed Abstract: Engineering biosynthetic pathways to ribosomally synthesized and post-translationally modified peptides (RiPPs) offers several advantages for both and applications. Here we probe the ability of peptide cyclases to generate trimacrocycle microviridin analogs with non-native cross-links. The results demonstrate that diverse chemistries are tolerated by macrocyclases in the ATP-grasp family and allow for the construction of unique cyclic peptide architectures that retain protease inhibition activity. In addition, cocomplex structures of analogs bound to a model protease were determined, illustrating how changes in functional groups maintain peptide conformation and target binding.

PubMed: 38306609
DOI: 10.1021/acs.orglett.3c04045

Experimental method

X-RAY DIFFRACTION (1.56 Å)