Database of articles cited by EMDB/PDB/SASBDB data

Keywords
Structure methods	All X-ray diffraction NMR electron microscopy small angle scattering neutron diffraction fiber diffraction powder diffraction infrared spectroscopy EPR fluorescence transfer theoretical model Hybrid
Author
Journal
IF	>30 >20 >10 >5 all

Title	Targeting imidazole-glycerol phosphate dehydratase in plants: novel approach for structural and functional studies, and inhibitor blueprinting.
Journal, issue, pages	Front Plant Sci, Vol. 15, Page 1343980, Year 2024
Publish date	Mar 15, 2024
Authors	Wojciech Witek / Joanna Sliwiak / Michal Rawski / Milosz Ruszkowski /
PubMed Abstract	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.
External links	Front Plant Sci / PubMed:38559763 / PubMed Central
Methods	EM (single particle) / X-ray diffraction
Resolution	1.55 - 2.4 Å
Structure data	12938 7oj5 EMDB-12938, PDB-7oj5: Cryo-EM structure of Medicago truncatula HISN5 protein Method: EM (single particle) / Resolution: 2.4 Å 18305 8qav EMDB-18305, PDB-8qav: Medicago truncatula HISN5 (IGPD) in complex with MN and IG2 Method: EM (single particle) / Resolution: 2.23 Å PDB-8qaw: Medicago truncatula HISN5 (IGPD) in complex with MN, IMD, EDO, FMT, GOL and TRS Method: X-RAY DIFFRACTION / Resolution: 1.55 Å PDB-8qax: Medicago truncatula HISN5 (IGPD) in complex with MN, FMT, GOL and TRS Method: X-RAY DIFFRACTION / Resolution: 1.69 Å PDB-8qay: Medicago truncatula HISN5 (IGPD) in complex with MN, FMT, ACT, CIT, EDO, SO4 Method: X-RAY DIFFRACTION / Resolution: 2.2 Å
Chemicals	ChemComp-MN: Unknown entry ChemComp-HOH: WATER ChemComp-IG2: (2S,3S)-2,3-dihydroxy-3-(1H-imidazol-5-yl)propyl dihydrogen phosphate ChemComp-IMD: IMIDAZOLE ChemComp-FMT: FORMIC ACID ChemComp-EDO: 1,2-ETHANEDIOL ChemComp-GOL: GLYCEROL ChemComp-TRS: 2-AMINO-2-HYDROXYMETHYL-PROPANE-1,3-DIOL / pH bufferYM ChemComp-CL: Unknown entry ChemComp-NA: Unknown entry ChemComp-CIT: CITRIC ACID ChemComp-SO4: SULFATE ION ChemComp-ACT*: ACETATE ION
Source	medicago truncatula (barrel medic)
Keywords	LYASE / histidine biosynthesis / herbicide design / high-resolution Cryo-EM / Medicago truncatula HISN5 IGPD histidine / HISN5 / IGPD / Medicago truncatula