6UTS

Crystal Structure of bacterial pirin YhhW in complex with nickel(II) from Escherichia coli

6UTS の概要

• エントリーDOI: 10.2210/pdb6uts/pdb
• 分子名称: Quercetin 2,3-dioxygenase, NICKEL (II) ION (2 entities in total)
• 機能のキーワード: bacterial pirin, nickel binding, quercetinase, metal binding protein, oxidoreductase
• 由来する生物種: Escherichia coli (strain K12)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 26369.06

構造登録者

Guo, B.,Zhang, Y.,Jia, Z. (登録日: 2019-10-29, 公開日: 2019-11-06, 最終更新日: 2023-10-11)

主引用文献

Guo, B.,Zhang, Y.,Hicks, G.,Huang, X.,Li, R.,Roy, N.,Jia, Z.
Structure-Dependent Modulation of Substrate Binding and Biodegradation Activity of Pirin Proteins toward Plant Flavonols.
Acs Chem.Biol., 14:2629-2640, 2019

PubMed Abstract: Pirin is a nonheme metalloprotein that occurs widely in human tissues and is highly conserved across all taxa. Pirin proteins typically function as nuclear transcription regulators, but two Pirin orthologs, YhhW (from ) and hPirin (from humans) were revealed to possess enzymatic activity of degrading quercetin. The exact role of Pirin homologues and their catalytic specificity remain poorly understood. In this work, by screening against a panel of plant flavonoids, we found that both Pirins catalyze the oxidative degradation of a wide spectrum of flavonol analogues and release carbon monoxide (CO) in the process. This shows that Pirin acts on a broad range of substrates and could represent a novel dietary source of CO . Although the kinetic profiles differ substantially between two Pirins, the identified substrate structures all share a 2,3-double bond and 3-hydroxyl and 4-oxo groups on their "flavonol backbone," which contribute to the specific enzyme-substrate interaction. While hPirin is iron-dependent, YhhW is identified as a novel nickel-containing dioxygenase member of the bicupin family. Besides the expanded Pirin activity, we present the crystal structures of the native Ni-YhhW and tag-free Fe-hPirin, revealing the distinctive differences occurring at the metal-binding site. In addition, YhhW features a flexible Ω-loop near the catalytic cavity, which may help stabilize the reaction intermediates via a Ni-flavonol complex. The structure-dependent modulation of substrate binding to the catalytic cavity adds to understanding the differential dispositions of natural flavonols by human and bacterial Pirins.

PubMed: 31609578
DOI: 10.1021/acschembio.9b00575

実験手法

X-RAY DIFFRACTION (3.09 Å)