1SQD

Structural basis for inhibitor selectivity revealed by crystal structures of plant and mammalian 4-hydroxyphenylpyruvate dioxygenases

1SQD の概要

• エントリーDOI: 10.2210/pdb1sqd/pdb
• 分子名称: 4-hydroxyphenylpyruvate dioxygenase, FE (III) ION (3 entities in total)
• 機能のキーワード: oxidoreductase
• 由来する生物種: Arabidopsis thaliana (thale cress)
• 細胞内の位置: Cytoplasm : P93836
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 46839.64

構造登録者

Yang, C.,Pflugrath, J.W.,Camper, D.L.,Foster, M.L.,Pernich, D.J.,Walsh, T.A. (登録日: 2004-03-18, 公開日: 2004-08-17, 最終更新日: 2024-10-16)

主引用文献

Yang, C.,Pflugrath, J.W.,Camper, D.L.,Foster, M.L.,Pernich, D.J.,Walsh, T.A.
Structural basis for herbicidal inhibitor selectivity revealed by comparison of crystal structures of plant and Mammalian 4-hydroxyphenylpyruvate dioxygenases
Biochemistry, 43:10414-10423, 2004

PubMed Abstract: A high degree of selectivity toward the target site of the pest organism is a desirable attribute for new safer agrochemicals. To assist in the design of novel herbicides, we determined the crystal structures of the herbicidal target enzyme 4-hydroxyphenylpyruvate dioxygenase (HPPD; EC 1.13.11.27) from the plant Arabidopsis thaliana with and without an herbicidal benzoylpyrazole inhibitor that potently inhibits both plant and mammalian HPPDs. We also determined the structure of a mammalian (rat) HPPD in complex with the same nonselective inhibitor. From a screening campaign of over 1000 HPPD inhibitors, six highly plant-selective inhibitors were found. One of these had remarkable (>1600-fold) selectivity toward the plant enzyme and was cocrystallized with Arabidopsis HPPD. Detailed comparisons of the plant and mammalian HPPD-ligand structures suggest a structural basis for the high degree of plant selectivity of certain HPPD inhibitors and point to design strategies to obtain potent and selective inhibitors of plant HPPD as agrochemical leads.

PubMed: 15301540
DOI: 10.1021/bi049323o

実験手法

X-RAY DIFFRACTION (1.8 Å)