雑誌会（200115）回答_藤田

Communication

Quercetin 2,4-Dioxygenase Activates Dioxygen in a Side-On O2–Ni Complex

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• Humboldt-University, Berlin
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• First published: 5 February 2016Full publication history
• DOI: 10.1002/anie.201510741View/save citation
• Cited by: 0 articles Check for new citations
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• Funding Information
• http://onlinelibrary.wiley.com/doi/10.1002/anie.201510741/epdf

Abstract

Quercetin 2,4-dioxygenase (quercetinase) from Streptomyces uses nickel as the active-site cofactor to catalyze oxidative cleavage of the flavonol quercetin. How this unusual active-site metal supports catalysis and O2 activation is under debate. We present crystal structures of Ni-quercetinase in three different states, thus providing direct insight into how quercetin and O2 are activated at the Ni2+ ion. The Ni2+ ion is coordinated by three histidine residues and a glutamate residue (E76) in all three states. Upon binding, quercetin replaces one water ligand at Ni and is stabilized by a short hydrogen bond through E76, the carboxylate group of which rotates by 90°. This conformational change weakens the interaction between Ni and the remaining water ligand, thereby preparing a coordination site at Ni to bind O2. O2 binds side-on to the Ni2+ ion and is perpendicular to the C2−C3 and C3−C4 bonds of quercetin, which are cleaved in the following reaction steps.

In this report, they present crystal structures of Ni-quercetinase in three different state (Free E [1.80 Å], ES-complex [2.15 Å ], ES:O2 complex [1.82 Å]), to show how quercetin and O2 are activated at the Ni2+ ion.

Quercetin replaces W1 at Ni and is stabilized by a short hydrogen bond through a glutamate regidue (E76), the carboxylate group of which rotates by 90º. This conformational change weakens the interaction between Ni and W2, thereby priming Ni2+ to bind O2 side-on and attack quercetin.

The mechanism is supported by the crystal structures.