6muj

Formylglycine generating enzyme bound to copper

spinqualitylabelsall models 6muj, resolution 2.25Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6muj is a 5 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 2.249Å Ligands: CA, CU, DTT, FMT, GLY, GOL, IMD Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function FGE_STRCO Oxidase that catalyzes the conversion of cysteine to 3-oxoalanine on target proteins. 3-oxoalanine modification, which is also named formylglycine (fGly), occurs in the maturation of arylsulfatases and some alkaline phosphatases that use the hydrated form of 3-oxoalanine as a catalytic nucleophile. Publication Abstract from PubMed The formylglycine-generating enzyme (FGE) is required for the posttranslational activation of type I sulfatases by oxidation of an active-site cysteine to Calpha-formylglycine. FGE has emerged as an enabling biotechnology tool due to the robust utility of the aldehyde product as a bioconjugation handle in recombinant proteins. Here, we show that Cu(I)-FGE is functional in O2 activation and reveal a high-resolution X-ray crystal structure of FGE in complex with its catalytic copper cofactor. We establish that the copper atom is coordinated by two active-site cysteine residues in a nearly linear geometry, supporting and extending prior biochemical and structural data. The active cuprous FGE complex was interrogated directly by X-ray absorption spectroscopy. These data unambiguously establish the configuration of the resting enzyme metal center and, importantly, reveal the formation of a three-coordinate tris(thiolate) trigonal planar complex upon substrate binding as furthermore supported by density functional theory (DFT) calculations. Critically, inner-sphere substrate coordination turns on O2 activation at the copper center. These collective results provide a detailed mechanistic framework for understanding why nature chose this structurally unique monocopper active site to catalyze oxidase chemistry for sulfatase activation. Formylglycine-generating enzyme binds substrate directly at a mononuclear Cu(I) center to initiate O2 activation.,Appel MJ, Meier KK, Lafrance-Vanasse J, Lim H, Tsai CL, Hedman B, Hodgson KO, Tainer JA, Solomon EI, Bertozzi CR Proc Natl Acad Sci U S A. 2019 Mar 1. pii: 1818274116. doi:, 10.1073/pnas.1818274116. PMID:30824597 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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