EMDB/PDB/SASBDBから引用されている文献のデータベース

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構造解析手法	All X線回折 NMR 電子顕微鏡小角散乱中性子線回折線維回折粉末回折赤外分光 EPR FRET 理論モデルハイブリッド
著者・登録者
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IF	>30 >20 >10 >5 all

タイトル	Cryo-EM structures demonstrate human IMPDH2 filament assembly tunes allosteric regulation.
ジャーナル・号・ページ	Elife, Vol. 9, Year 2020
掲載日	2020年1月30日
著者	Matthew C Johnson / Justin M Kollman /
PubMed 要旨	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.
リンク	Elife / PubMed:31999252 / PubMed Central
手法	EM (単粒子)
解像度	2.95 - 7.13 Å
構造データ	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. 手法: EM (単粒子) / 解像度: 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. 手法: EM (単粒子) / 解像度: 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. 手法: EM (単粒子) / 解像度: 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. 手法: EM (単粒子) / 解像度: 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. 手法: EM (単粒子) / 解像度: 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. 手法: EM (単粒子) / 解像度: 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. 手法: EM (単粒子) / 解像度: 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. 手法: EM (単粒子) / 解像度: 3.79 Å 20707 6uaj EMDB-20707, PDB-6uaj: Human IMPDH2 treated with ATP, IMP, NAD+, and 2 mM GTP. Free canonical octamer reconstruction. 手法: EM (単粒子) / 解像度: 3.84 Å EMDB-20709: Human IMPDH2 treated with ATP and NAD+. Fully compressed filament segment reconstruction. 手法: EM (単粒子) / 解像度: 4.5 Å EMDB-20716: Human IMPDH2 treated with ATP and NAD+. Fully extended filament segment reconstruction. 手法: EM (単粒子) / 解像度: 4.53 Å EMDB-20718: Human IMPDH2 treated with ATP and NAD+. Filament assembly interface reconstruction. 手法: EM (単粒子) / 解像度: 4.05 Å EMDB-20720: Human IMPDH2 treated with ATP and IMP. Fully compressed filament segment reconstruction. 手法: EM (単粒子) / 解像度: 7.13 Å EMDB-20722: Human IMPDH2 treated with ATP and IMP. Fully extended filament segment reconstruction. 手法: EM (単粒子) / 解像度: 7.13 Å EMDB-20723: Human IMPDH2 treated with ATP and IMP. Filament assembly interface reconstruction. 手法: EM (単粒子) / 解像度: 4.42 Å 20725 6uc2 EMDB-20725, PDB-6uc2: Human IMPDH2 treated with ATP and 2 mM GTP. Free canonical octamer reconstruction. 手法: EM (単粒子) / 解像度: 4.48 Å 20741 6udo EMDB-20741, PDB-6udo: Human IMPDH2 treated with ATP, IMP, and 20 mM GTP. Fully compressed filament segment reconstruction. 手法: EM (単粒子) / 解像度: 3.21 Å 20742 6udp EMDB-20742, PDB-6udp: Human IMPDH2 treated with ATP, IMP, and 20 mM GTP. Filament assembly interface reconstruction. 手法: EM (単粒子) / 解像度: 2.95 Å 20743 6udq EMDB-20743, PDB-6udq: Human IMPDH2 treated with ATP, IMP, and 20 mM GTP. Fully compressed filament end reconstruction. 手法: EM (単粒子) / 解像度: 3.27 Å
化合物	ChemComp-IMP: INOSINIC ACID / IMP / イノシン酸 ChemComp-NAD: NICOTINAMIDE-ADENINE-DINUCLEOTIDE / NADYM / ニコチンアミドアデニンジヌクレオチド ChemComp-ATP: ADENOSINE-5'-TRIPHOSPHATE / ATP / ATP, エネルギー貯蔵分子YM / アデノシン三リン酸 ChemComp-GTP: GUANOSINE-5'-TRIPHOSPHATE / GTP / GTP, エネルギー貯蔵分子*YM / グアノシン三リン酸
由来	homo sapiens (ヒト)
キーワード	BIOSYNTHETIC PROTEIN (生合成) / metabolism (代謝) / filament / allostery (アロステリック効果) / adenine (アデニン) / guanine (グアニン)