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-基本情報
登録情報 | データベース: PDB / ID: 8qav | ||||||
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タイトル | Medicago truncatula HISN5 (IGPD) in complex with MN and IG2 | ||||||
要素 | Imidazoleglycerol-phosphate dehydratase | ||||||
キーワード | LYASE (リアーゼ) / Medicago truncatula HISN5 IGPD histidine | ||||||
機能・相同性 | 機能・相同性情報 imidazoleglycerol-phosphate dehydratase / imidazoleglycerol-phosphate dehydratase activity / L-histidine biosynthetic process 類似検索 - 分子機能 | ||||||
生物種 | Medicago truncatula (タルウマゴヤシ) | ||||||
手法 | 電子顕微鏡法 / 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度: 2.23 Å | ||||||
データ登録者 | Witek, W. / Ruszkowski, M. | ||||||
資金援助 | ポーランド, 1件
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引用 | ジャーナル: Front Plant Sci / 年: 2024 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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-構造の表示
構造ビューア | 分子: MolmilJmol/JSmol |
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-ダウンロードとリンク
-ダウンロード
PDBx/mmCIF形式 | 8qav.cif.gz | 1 MB | 表示 | PDBx/mmCIF形式 |
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PDB形式 | pdb8qav.ent.gz | 706.1 KB | 表示 | PDB形式 |
PDBx/mmJSON形式 | 8qav.json.gz | ツリー表示 | PDBx/mmJSON形式 | |
その他 | その他のダウンロード |
-検証レポート
アーカイブディレクトリ | https://data.pdbj.org/pub/pdb/validation_reports/qa/8qav ftp://data.pdbj.org/pub/pdb/validation_reports/qa/8qav | HTTPS FTP |
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非結晶学的対称性 (NCS) | NCSドメイン:
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