3AU8

Crystal structure of the ternary complex of an isomerase

3AU8 の概要

• エントリーDOI: 10.2210/pdb3au8/pdb
• 関連するPDBエントリー: 3AU9 3AUA
• 分子名称: 1-deoxy-D-xylulose 5-phosphate reductoisomerase, NADPH DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE, MANGANESE (II) ION, ... (4 entities in total)
• 機能のキーワード: nadph binding, isomerase
• 由来する生物種: Plasmodium falciparum
• 細胞内の位置: Plastid, apicoplast: O96693
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 113259.94

構造登録者

Umeda, T.,Tanaka, N.,Kusakabe, Y.,Nakanishi, M.,Kitade, Y.,Nakamura, K.T. (登録日: 2011-02-01, 公開日: 2011-08-10, 最終更新日: 2023-11-01)

主引用文献

Umeda, T.,Tanaka, N.,Kusakabe, Y.,Nakanishi, M.,Kitade, Y.,Nakamura, K.T.
Molecular basis of fosmidomycin's action on the human malaria parasite Plasmodium falciparum
Sci Rep, 1:9-9, 2011

PubMed Abstract: The human malaria parasite Plasmodium falciparum is responsible for the deaths of more than a million people each year. Fosmidomycin has been proven to be efficient in the treatment of P. falciparum malaria by inhibiting 1-deoxy-D-xylulose 5-phosphate reductoisomerase (DXR), an enzyme of the non-mevalonate pathway, which is absent in humans. However, the structural details of DXR inhibition by fosmidomycin in P. falciparum are unknown. Here, we report the crystal structures of fosmidomycin-bound complete quaternary complexes of PfDXR. Our study revealed that (i) an intrinsic flexibility of the PfDXR molecule accounts for an induced-fit movement to accommodate the bound inhibitor in the active site and (ii) a cis arrangement of the oxygen atoms of the hydroxamate group of the bound inhibitor is essential for tight binding of the inhibitor to the active site metal. We expect the present structures to be useful guides for the design of more effective antimalarial compounds.

PubMed: 22355528
DOI: 10.1038/srep00009

実験手法

X-RAY DIFFRACTION (1.86 Å)