6peu | pdb_00006peu

Structure of YcaO enzyme from Methanocaldococcus jannaschii in complex with peptide

spinqualitylabelsall models 6peu, resolution 1.95Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6peu is a 8 chain structure with sequence from Metja. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: ATP, MG Related: 6pe3 Gene: MJ1094 (METJA) Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed YcaO enzymes are known to catalyze the ATP-dependent formation of azoline heterocycles, thioamides, and (macro)lactamidines on peptide substrates. These enzymes are found in multiple biosynthetic pathways, including those for several different classes of ribosomally synthesized and post-translationally modified peptides (RiPPs). However, there are major knowledge gaps in the mechanistic and structural underpinnings that govern each of the known YcaO-mediated modifications. Here, we present the first structure of any YcaO enzyme bound to its peptide substrate in the active site, specifically that from Methanocaldococcus jannaschii which is involved in the thioamidation of the alpha-subunit of methyl-coenzyme M reductase (McrA). The structural data are leveraged to identify and test the residues involved in substrate binding and catalysis by site-directed mutagenesis. We also show that thioamide-forming YcaOs can carry out the cyclodehydration of a related peptide substrate, which underscores the mechanistic conservation across the YcaO family and allows for the extrapolation of mechanistic details to azoline-forming YcaOs involved in RiPP biosynthesis. A bioinformatic survey of all YcaOs highlights the diverse sequence space in azoline-forming YcaOs and suggests their early divergence from a common ancestor. The data presented within provide a detailed molecular framework for understanding this family of enzymes, which reconcile several decades of prior data on RiPP cyclodehydratases. These studies also provide the foundational knowledge to impact our mechanistic understanding of additional RiPP biosynthetic classes. Mechanistic Basis for Ribosomal Peptide Backbone Modifications.,Dong SH, Liu A, Mahanta N, Mitchell DA, Nair SK ACS Cent Sci. 2019 May 22;5(5):842-851. doi: 10.1021/acscentsci.9b00124. Epub, 2019 Apr 16. PMID:31139720 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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