5uzw

PCY1 G696Insertion Variant in Complex with Follower Peptide and the Covalent Inhibitor ZPP

spinqualitylabelsall models 5uzw, resolution 2.82Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5uzw is a 8 chain structure with sequence from Gypsophila vaccaria. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.82Å Ligands: CA, ZPR Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function R4P353_GYPVA Publication Abstract from PubMed Enzymes that can catalyze the macrocyclization of linear peptide substrates have long been sought for the production of libraries of structurally diverse scaffolds via combinatorial gene assembly as well as to afford rapid in vivo screening methods. Orbitides are plant ribosomally synthesized and posttranslationally modified peptides (RiPPs) of various sizes and topologies, several of which are shown to be biologically active. The diversity in size and sequence of orbitides suggests that the corresponding macrocyclases may be ideal catalysts for production of cyclic peptides. Here we present the biochemical characterization and crystal structures of the plant enzyme PCY1 involved in orbitide macrocyclization. These studies demonstrate how the PCY1 S9A protease fold has been adapted for transamidation, rather than hydrolysis, of acyl-enzyme intermediates to yield cyclic products. Notably, PCY1 uses an unusual strategy in which the cleaved C-terminal follower peptide from the substrate stabilizes the enzyme in a productive conformation to facilitate macrocyclization of the N-terminal fragment. The broad substrate tolerance of PCY1 can be exploited as a biotechnological tool to generate structurally diverse arrays of macrocycles, including those with nonproteinogenic elements. Characterization of the macrocyclase involved in the biosynthesis of RiPP cyclic peptides in plants.,Chekan JR, Estrada P, Covello PS, Nair SK Proc Natl Acad Sci U S A. 2017 Jun 20;114(25):6551-6556. doi:, 10.1073/pnas.1620499114. Epub 2017 Jun 5. PMID:28584123 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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