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.

6S07 の概要

• エントリーDOI: 10.2210/pdb6s07/pdb
• 分子名称: 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)
• 機能のキーワード: formylglycine-generating enzyme, complex, substrate analog, copper, transferase
• 由来する生物種: Thermomonospora curvata (strain ATCC 19995 / DSM 43183 / JCM 3096 / NBRC 15933 / NCIMB 10081 / Henssen B9); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 35166.88

構造登録者

Leisinger, F.,Miarzlou, D.A.,Seebeck, F.P. (登録日: 2019-06-14, 公開日: 2019-06-26, 最終更新日: 2024-01-24)

主引用文献

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

実験手法

X-RAY DIFFRACTION (1.04 Å)