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基本情報
登録情報 | データベース: PDB / ID: 8qay | ||||||
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タイトル | Medicago truncatula HISN5 (IGPD) in complex with MN, FMT, ACT, CIT, EDO, SO4 | ||||||
![]() | Imidazoleglycerol-phosphate dehydratase | ||||||
![]() | LYASE / HISN5 / IGPD / histidine biosynthesis / Medicago truncatula | ||||||
機能・相同性 | ![]() imidazoleglycerol-phosphate dehydratase / imidazoleglycerol-phosphate dehydratase activity / L-histidine biosynthetic process 類似検索 - 分子機能 | ||||||
生物種 | ![]() ![]() | ||||||
手法 | ![]() ![]() | ||||||
![]() | Witek, W. / Ruszkowski, M. | ||||||
資金援助 | ![]()
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![]() | ![]() タイトル: Targeting imidazole-glycerol phosphate dehydratase in plants: novel approach for structural and functional studies, and inhibitor blueprinting. 著者: Wojciech Witek / Joanna Sliwiak / Michal Rawski / Milosz Ruszkowski / ![]() 要旨: The histidine biosynthetic pathway (HBP) is targeted for herbicide design with preliminary success only regarding imidazole-glycerol phosphate dehydratase (IGPD, EC 4.2.1.19), or HISN5, as referred ...The histidine biosynthetic pathway (HBP) is targeted for herbicide design with preliminary success only regarding imidazole-glycerol phosphate dehydratase (IGPD, EC 4.2.1.19), or HISN5, as referred to in plants. HISN5 catalyzes the sixth step of the HBP, in which imidazole-glycerol phosphate (IGP) is dehydrated to imidazole-acetol phosphate. In this work, we present high-resolution cryoEM and crystal structures of HISN5 (HISN5) in complexes with an inactive IGP diastereoisomer and with various other ligands. HISN5 can serve as a new model for plant HISN5 structural studies, as it enables resolving protein-ligand interactions at high (2.2 Å) resolution using cryoEM. We identified ligand-binding hotspots and characterized the features of plant HISN5 enzymes in the context of the HISN5-targeted inhibitor design. Virtual screening performed against millions of small molecules not only revealed candidate molecules but also identified linkers for fragments that were experimentally confirmed to bind. Based on experimental and computational approaches, this study provides guidelines for designing symmetric HISN5 inhibitors that can reach two neighboring active sites. Finally, we conducted analyses of sequence similarity networks revealing that plant HISN5 enzymes derive from cyanobacteria. We also adopted a new approach to measure HISN5 enzymatic activity using isothermal titration calorimetry and enzymatically synthesized IGP. | ||||||
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-関連構造データ
関連構造データ | ![]() 8qavC ![]() 8qawC ![]() 8qaxC C: 同じ文献を引用 ( |
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非結晶学的対称性 (NCS) | NCSドメイン:
NCSドメイン領域: Ens-ID: ens_1
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