6S07

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.

Summary for 6S07

• Entry DOI: 10.2210/pdb6s07/pdb
• Descriptor: Formylglycine-generating enzyme, Abz-ALA-THR-THR-PRO-LEU-CYS-GLY-PRO-SER-ARG-ALA-SER-ILE-LEU-SER-GLY-ARG, COPPER (I) ION, ... (6 entities in total)
• Functional Keywords: formylglycine-generating enzyme, complex, substrate analog, copper, transferase
• Biological source: Thermomonospora curvata (strain ATCC 19995 / DSM 43183 / JCM 3096 / NBRC 15933 / NCIMB 10081 / Henssen B9); More
• Total number of polymer chains: 2
• Total formula weight: 35166.88

Authors

Leisinger, F.,Miarzlou, D.A.,Seebeck, F.P. (deposition date: 2019-06-14, release date: 2019-06-26, Last modification date: 2024-01-24)

Primary citation

Miarzlou, D.A.,Leisinger, F.,Joss, D.,Haussinger, D.,Seebeck, F.P.
Structure of formylglycine-generating enzyme in complex with copper and a substrate reveals an acidic pocket for binding and activation of molecular oxygen.
Chem Sci, 10:7049-7058, 2019

PubMed Abstract: The formylglycine generating enzyme (FGE) catalyzes oxidative conversion of specific peptidyl-cysteine residues to formylglycine. FGE mediates O-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 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-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-binding and subsequent activation.

PubMed: 31588272
DOI: 10.1039/c9sc01723b

Experimental method

X-RAY DIFFRACTION (1.04 Å)