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Structure of formylglycine-generating enzyme in complex with copper and a substrate reveals an acidic pocket for binding and activation of molecular oxygen

Miarzlou, Dzmitry A. and Leisinger, Florian and Joss, Daniel and Häussinger, Daniel and Seebeck, Florian P.. (2019) Structure of formylglycine-generating enzyme in complex with copper and a substrate reveals an acidic pocket for binding and activation of molecular oxygen. Chemical Science, 10 (29). pp. 7049-7058.

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Abstract

The formylglycine generating enzyme (FGE) catalyzes oxidative conversion of specific peptidyl-cysteine residues to formylglycine. FGE mediates O; 2; -activation and hydrogen-atom abstraction in an active site that contains Cu(i) coordinated to two cysteine residues. Similar coordination geometries are common among copper-sensing transcription factors and copper-chaperone but are unprecedented among copper-dependent oxidases. To examine the mechanism of this unusual catalyst we determined the 1.04 Å structure of FGE from; Thermomonospora curvata; in complex with copper and a cysteine-containing peptide substrate. This structure unveils a network of four crystallographic waters and two active site residues that form a highly acidic O; 2; -binding pocket juxtaposed to the trigonal planar tris-cysteine coordinated Cu(i) center. Comparison with structures of FGE in complex with Ag(i) and Cd(ii) combined with evidence from NMR spectroscopy and kinetic observations highlight several structural changes that are induced by substrate binding and prime the enzyme for O; 2; -binding and subsequent activation.
Faculties and Departments:05 Faculty of Science > Departement Chemie > Chemie > Molecular Bionics (Seebeck)
05 Faculty of Science > Departement Chemie > Chemie > Nuclear Magnetic Resonance (Häussinger)
UniBasel Contributors:Seebeck, Florian Peter and Häussinger, Daniel
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:Royal Society of Chemistry
ISSN:2041-6520
e-ISSN:2041-6539
Note:Publication type according to Uni Basel Research Database: Journal article
Language:English
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Last Modified:05 Feb 2020 15:04
Deposited On:05 Feb 2020 15:04

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