1XI2

Quinone Reductase 2 in Complex with Cancer Prodrug CB1954

1XI2 の概要

• エントリーDOI: 10.2210/pdb1xi2/pdb
• 関連するPDBエントリー: 1QR2 2QR2
• 分子名称: NRH dehydrogenase [quinone] 2, ZINC ION, FLAVIN-ADENINE DINUCLEOTIDE, ... (5 entities in total)
• 機能のキーワード: qr2, cb1954, oxidoreductase
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 53970.37

構造登録者

Fu, Y.,Buryanovskyy, L.,Zhang, Z. (登録日: 2004-09-21, 公開日: 2005-08-30, 最終更新日: 2024-02-14)

主引用文献

Fu, Y.,Buryanovskyy, L.,Zhang, Z.
Crystal structure of quinone reductase 2 in complex with cancer prodrug CB1954
Biochem.Biophys.Res.Commun., 336:332-338, 2005

PubMed Abstract: CB1954 is a cancer pro-drug that can be activated through reduction by Escherichia coli nitro-reductases and quinone reductases. Human quinone reductase 2 is very efficient in the activation of CB1954, approximately 3000 times more efficient than human QR1 in terms of k(cat)/K(m). We have solved the three-dimensional structure of QR2 in complex with CB1954 to a nominal resolution of 1.5A. The complex structure indicates the essentiality of the two nitro groups: one nitro group forms hydrogen bonds with the side-chain of Asn161 of QR2 to hold the other nitro group in position for the reduction. We further conclude that residue 161, an Asn in QR2 and a His in QR1, is critical in differentiating the substrate specificities of these two enzymes. Mutation of Asn161 to His161 in QR2 resulted in the total loss of the enzymatic activity towards activation of CB1954, whereas the rates of reduction towards menadione are not altered.

PubMed: 16129418
DOI: 10.1016/j.bbrc.2005.08.081

実験手法

X-RAY DIFFRACTION (1.5 Å)