6s07
From Proteopedia
Structure of formylglycine-generating enzyme at 1.04 A in complex with copper and substrate reveals an acidic pocket for binding and acti-vation of molecular oxygen.
Structural highlights
FunctionFGE_THECD 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.[1] [2] Publication Abstract from PubMedThe formylglycine generating enzyme (FGE) catalyzes oxidative conversion of specific peptidyl-cysteine residues to formylglycine. FGE mediates O2-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 A 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 O2-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 O2-binding and subsequent activation. Structure of formylglycine-generating enzyme in complex with copper and a substrate reveals an acidic pocket for binding and activation of molecular oxygen.,Miarzlou DA, Leisinger F, Joss D, Haussinger D, Seebeck FP Chem Sci. 2019 Jun 18;10(29):7049-7058. doi: 10.1039/c9sc01723b. eCollection 2019, Aug 7. PMID:31588272[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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