9bou

Crystal structure of ATP-grasp ligase PruB from Streptomyces coelicolor A3(2)

spinqualitylabelsall models 9bou, resolution 2.91Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 9bou is a 2 chain structure with sequence from Streptomyces coelicolor A3(2). Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.91Å Ligands: SO4 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function Q9L2K8_STRCO Publication Abstract from PubMed Graspetides are a diverse family of ribosomally synthesized and post-translationally modified peptides with unique macrocyclic structures formed by ATP-grasp enzymes. Group 11 graspetides, including prunipeptin, feature both macrolactone and macrolactam cross-links. Despite the known involvement of a single ATP-grasp cyclase in the dual macrocyclizations of groups 5, 7, and 11 graspetides, detailed mechanistic insights into these enzymes remain limited. Here, we reconstructed prunipeptin biosynthesis from Streptomyces coelicolor using recombinant PruA and PruB macrocyclase. PruB exhibited kinetic behavior similar to other characterized graspetide cyclases, with a notably higher k(cat), likely due to utilization of an ATP-regeneration system. The X-ray crystal structure of PruB revealed distinct features as compared to groups 1 and 2 enzymes. Site-directed mutagenesis identified critical roles of key residues for the PruB reaction, including the DxR motif conserved in other graspetide cyclases. Additionally, computational modeling of the PruA/PruB cocomplex uncovered substrate interactions and suggested that PruB first catalyzes a macrolactone bond formation on PruA. This study enhances our understanding of ATP-grasp enzyme mechanisms in graspetide biosynthesis and provides insights for engineering these enzymes for future applications. Characterization of a Dual Function Peptide Cyclase in Graspetide Biosynthesis.,Rubin GM, Patel KP, Jiang Y, Ishee AC, Seabra G, Bruner SD, Ding Y ACS Chem Biol. 2024 Dec 4. doi: 10.1021/acschembio.4c00626. PMID:39630567 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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