9fce

BelI in complex with SAM from Streptomyces sp. UCK14

spinqualitylabelsall models 9fce, resolution 1.95Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 9fce is a 2 chain structure with sequence from Streptomyces sp.. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.95Å Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function A0A1W6R583_STRSQ Publication Abstract from PubMed Cystargolides and belactosins are natural products with a distinct dipeptide structure and an electrophilic beta-lactone warhead. They are known to inhibit proteases such as the proteasome or caseinolytic protease P, highlighting their potential in treating cancers and neurodegenerative diseases. Recent genetic analyses have shown homology between the biosynthetic pathways of the two inhibitors. Here, we characterize the O-methyltransferases BelI and CysG, which catalyze the initial step of beta-lactone formation. Employing techniques such as crystallography, computational analysis, mutagenesis, and activity assays, we identified a His-His-Asp (HHD) motif in the active sites of the two enzymes, which is crucial for binding a catalytically active calcium ion. Our findings thus elucidate a conserved divalent metal-dependent mechanism in both biosynthetic pathways that distinguishes BelI and CysG from previously characterized O-methyltransferases. Deciphering the SAM- and Metal-Dependent Mechanism of O-Methyltransferases in Cystargolide and Belactosin Biosynthesis: A Structure-Activity Relationship Study.,Kuttenlochner W, Beller P, Kaysser L, Groll M J Biol Chem. 2024 Aug 7:107646. doi: 10.1016/j.jbc.2024.107646. PMID:39121999 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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