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	Cryo-EM structures demonstrate human IMPDH2 filament assembly tunes allosteric regulation.
Journal, issue, pages	Elife, Vol. 9, Year 2020
Publish date	Jan 30, 2020
Authors	Matthew C Johnson / Justin M Kollman /
PubMed Abstract	Inosine monophosphate dehydrogenase (IMPDH) mediates the first committed step in guanine nucleotide biosynthesis and plays important roles in cellular proliferation and the immune response. IMPDH ...Inosine monophosphate dehydrogenase (IMPDH) mediates the first committed step in guanine nucleotide biosynthesis and plays important roles in cellular proliferation and the immune response. IMPDH reversibly polymerizes in cells and tissues in response to changes in metabolic demand. Self-assembly of metabolic enzymes is increasingly recognized as a general mechanism for regulating activity, typically by stabilizing specific conformations of an enzyme, but the regulatory role of IMPDH filaments has remained unclear. Here, we report a series of human IMPDH2 cryo-EM structures in both active and inactive conformations. The structures define the mechanism of filament assembly, and reveal how filament-dependent allosteric regulation of IMPDH2 makes the enzyme less sensitive to feedback inhibition, explaining why assembly occurs under physiological conditions that require expansion of guanine nucleotide pools. Tuning sensitivity to an allosteric inhibitor distinguishes IMPDH from other metabolic filaments, and highlights the diversity of regulatory outcomes that can emerge from self-assembly.
External links	Elife / PubMed:31999252 / PubMed Central
Methods	EM (single particle)
Resolution	2.95 - 7.13 Å
Structure data	20687 6u8e 6ua2 6ua5 6uaj EMDB-20687, PDB-6u8e: Human IMPDH2 treated with ATP, IMP, and NAD+. Filament assembly interface reconstruction. PDB-6ua2: Human IMPDH2 treated with ATP, IMP, NAD+, and 2 mM GTP. Bent (2/4 compressed, 2/4 extended) segment reconstruction. PDB-6ua5: Human IMPDH2 treated with ATP, IMP, NAD+, and 2 mM GTP. Free interfacial octamer reconstruction. PDB-6uaj: Human IMPDH2 treated with ATP, IMP, NAD+, and 2 mM GTP. Free canonical octamer reconstruction. Method: EM (single particle) / Resolution: 3.03 Å 20688 6u8n 6ua2 6ua5 6uaj EMDB-20688, PDB-6u8n: Human IMPDH2 treated with ATP, IMP, and NAD+. Fully extended filament segment reconstruction. PDB-6ua2: Human IMPDH2 treated with ATP, IMP, NAD+, and 2 mM GTP. Bent (2/4 compressed, 2/4 extended) segment reconstruction. PDB-6ua5: Human IMPDH2 treated with ATP, IMP, NAD+, and 2 mM GTP. Free interfacial octamer reconstruction. PDB-6uaj: Human IMPDH2 treated with ATP, IMP, NAD+, and 2 mM GTP. Free canonical octamer reconstruction. Method: EM (single particle) / Resolution: 3.29 Å 20690 6u8r 6ua2 6ua5 6uaj EMDB-20690, PDB-6u8r: Human IMPDH2 treated with ATP, IMP, and NAD+. Bent (1/4 compressed, 3/4 extended) segment reconstruction. PDB-6ua2: Human IMPDH2 treated with ATP, IMP, NAD+, and 2 mM GTP. Bent (2/4 compressed, 2/4 extended) segment reconstruction. PDB-6ua5: Human IMPDH2 treated with ATP, IMP, NAD+, and 2 mM GTP. Free interfacial octamer reconstruction. PDB-6uaj: Human IMPDH2 treated with ATP, IMP, NAD+, and 2 mM GTP. Free canonical octamer reconstruction. Method: EM (single particle) / Resolution: 3.91 Å 20691 6u8s 6ua2 6ua5 6uaj EMDB-20691, PDB-6u8s: Human IMPDH2 treated with ATP, IMP, NAD+, and 2 mM GTP. Filament assembly interface reconstruction. PDB-6ua2: Human IMPDH2 treated with ATP, IMP, NAD+, and 2 mM GTP. Bent (2/4 compressed, 2/4 extended) segment reconstruction. PDB-6ua5: Human IMPDH2 treated with ATP, IMP, NAD+, and 2 mM GTP. Free interfacial octamer reconstruction. PDB-6uaj: Human IMPDH2 treated with ATP, IMP, NAD+, and 2 mM GTP. Free canonical octamer reconstruction. Method: EM (single particle) / Resolution: 3.14 Å 20701 6u9o 6ua2 6ua5 6uaj EMDB-20701, PDB-6u9o: Human IMPDH2 treated with ATP, IMP, NAD+, and 2 mM GTP. Fully compressed filament segment reconstruction. PDB-6ua2: Human IMPDH2 treated with ATP, IMP, NAD+, and 2 mM GTP. Bent (2/4 compressed, 2/4 extended) segment reconstruction. PDB-6ua5: Human IMPDH2 treated with ATP, IMP, NAD+, and 2 mM GTP. Free interfacial octamer reconstruction. PDB-6uaj: Human IMPDH2 treated with ATP, IMP, NAD+, and 2 mM GTP. Free canonical octamer reconstruction. Method: EM (single particle) / Resolution: 3.36 Å 20704 6ua2 6ua5 6uaj EMDB-20704, PDB-6ua2: Human IMPDH2 treated with ATP, IMP, NAD+, and 2 mM GTP. Bent (2/4 compressed, 2/4 extended) segment reconstruction. PDB-6ua5: Human IMPDH2 treated with ATP, IMP, NAD+, and 2 mM GTP. Free interfacial octamer reconstruction. PDB-6uaj: Human IMPDH2 treated with ATP, IMP, NAD+, and 2 mM GTP. Free canonical octamer reconstruction. Method: EM (single particle) / Resolution: 4.2 Å 20705 6ua4 6ua5 6uaj EMDB-20705, PDB-6ua4: Human IMPDH2 treated with ATP, IMP, NAD+, and 2 mM GTP. Bent (3/4 compressed, 1/4 extended) segment reconstruction. PDB-6ua5: Human IMPDH2 treated with ATP, IMP, NAD+, and 2 mM GTP. Free interfacial octamer reconstruction. PDB-6uaj: Human IMPDH2 treated with ATP, IMP, NAD+, and 2 mM GTP. Free canonical octamer reconstruction. Method: EM (single particle) / Resolution: 3.65 Å 20706 6ua5 6uaj EMDB-20706, PDB-6ua5: Human IMPDH2 treated with ATP, IMP, NAD+, and 2 mM GTP. Free interfacial octamer reconstruction. PDB-6uaj: Human IMPDH2 treated with ATP, IMP, NAD+, and 2 mM GTP. Free canonical octamer reconstruction. Method: EM (single particle) / Resolution: 3.79 Å 20707 6uaj EMDB-20707, PDB-6uaj: Human IMPDH2 treated with ATP, IMP, NAD+, and 2 mM GTP. Free canonical octamer reconstruction. Method: EM (single particle) / Resolution: 3.84 Å EMDB-20709: Human IMPDH2 treated with ATP and NAD+. Fully compressed filament segment reconstruction. Method: EM (single particle) / Resolution: 4.5 Å EMDB-20716: Human IMPDH2 treated with ATP and NAD+. Fully extended filament segment reconstruction. Method: EM (single particle) / Resolution: 4.53 Å EMDB-20718: Human IMPDH2 treated with ATP and NAD+. Filament assembly interface reconstruction. Method: EM (single particle) / Resolution: 4.05 Å EMDB-20720: Human IMPDH2 treated with ATP and IMP. Fully compressed filament segment reconstruction. Method: EM (single particle) / Resolution: 7.13 Å EMDB-20722: Human IMPDH2 treated with ATP and IMP. Fully extended filament segment reconstruction. Method: EM (single particle) / Resolution: 7.13 Å EMDB-20723: Human IMPDH2 treated with ATP and IMP. Filament assembly interface reconstruction. Method: EM (single particle) / Resolution: 4.42 Å 20725 6uc2 EMDB-20725, PDB-6uc2: Human IMPDH2 treated with ATP and 2 mM GTP. Free canonical octamer reconstruction. Method: EM (single particle) / Resolution: 4.48 Å 20741 6udo EMDB-20741, PDB-6udo: Human IMPDH2 treated with ATP, IMP, and 20 mM GTP. Fully compressed filament segment reconstruction. Method: EM (single particle) / Resolution: 3.21 Å 20742 6udp EMDB-20742, PDB-6udp: Human IMPDH2 treated with ATP, IMP, and 20 mM GTP. Filament assembly interface reconstruction. Method: EM (single particle) / Resolution: 2.95 Å 20743 6udq EMDB-20743, PDB-6udq: Human IMPDH2 treated with ATP, IMP, and 20 mM GTP. Fully compressed filament end reconstruction. Method: EM (single particle) / Resolution: 3.27 Å
Chemicals	ChemComp-IMP: INOSINIC ACID ChemComp-NAD: NICOTINAMIDE-ADENINE-DINUCLEOTIDE / NADYM ChemComp-ATP: ADENOSINE-5'-TRIPHOSPHATE / ATP, energy-carrying moleculeYM ChemComp-GTP: GUANOSINE-5'-TRIPHOSPHATE / GTP, energy-carrying molecule*YM
Source	homo sapiens (human)
Keywords	BIOSYNTHETIC PROTEIN / metabolism / filament / allostery / adenine / guanine