EMDB/PDB/SASBDBから引用されている文献のデータベース

キーワード
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
ジャーナル
IF	>30 >20 >10 >5 all

タイトル	Using Cryo-EM to Map Small Ligands on Dynamic Metabolic Enzymes: Studies with Glutamate Dehydrogenase.
ジャーナル・号・ページ	Mol Pharmacol, Vol. 89, Issue 6, Page 645-651, Year 2016
掲載日	2016年4月1日
著者	Mario J Borgnia / Soojay Banerjee / Alan Merk / Doreen Matthies / Alberto Bartesaghi / Prashant Rao / Jason Pierson / Lesley A Earl / Veronica Falconieri / Sriram Subramaniam / Jacqueline L S Milne /
PubMed 要旨	Cryo-electron microscopy (cryo-EM) methods are now being used to determine structures at near-atomic resolution and have great promise in molecular pharmacology, especially in the context of mapping ...Cryo-electron microscopy (cryo-EM) methods are now being used to determine structures at near-atomic resolution and have great promise in molecular pharmacology, especially in the context of mapping the binding of small-molecule ligands to protein complexes that display conformational flexibility. We illustrate this here using glutamate dehydrogenase (GDH), a 336-kDa metabolic enzyme that catalyzes the oxidative deamination of glutamate. Dysregulation of GDH leads to a variety of metabolic and neurologic disorders. Here, we report near-atomic resolution cryo-EM structures, at resolutions ranging from 3.2 Å to 3.6 Å for GDH complexes, including complexes for which crystal structures are not available. We show that the binding of the coenzyme NADH alone or in concert with GTP results in a binary mixture in which the enzyme is in either an "open" or "closed" state. Whereas the structure of NADH in the active site is similar between the open and closed states, it is unexpectedly different at the regulatory site. Our studies thus demonstrate that even in instances when there is considerable structural information available from X-ray crystallography, cryo-EM methods can provide useful complementary insights into regulatory mechanisms for dynamic protein complexes.
リンク	Mol Pharmacol / PubMed:27036132 / PubMed Central
手法	EM (単粒子)
解像度	3.26 - 3.6 Å
構造データ	6630 3jcz EMDB-6630: Glutamate dehydrogenase in the unliganded state PDB-3jcz: Structure of bovine glutamate dehydrogenase in the unliganded state 手法: EM (単粒子) / 解像度: 3.26 Å 6631 3jd0 EMDB-6631, PDB-3jd0: Glutamate dehydrogenase in complex with GTP 手法: EM (単粒子) / 解像度: 3.47 Å 6632 3jd3 EMDB-6632, PDB-3jd3: Glutamate dehydrogenase in complex with NADH and GTP, open conformation 手法: EM (単粒子) / 解像度: 3.6 Å 6633 3jd4 EMDB-6633, PDB-3jd4: Glutamate dehydrogenase in complex with NADH and GTP, closed conformation 手法: EM (単粒子) / 解像度: 3.4 Å 6634 3jd1 EMDB-6634, PDB-3jd1: Glutamate dehydrogenase in complex with NADH, closed conformation 手法: EM (単粒子) / 解像度: 3.3 Å 6635 3jd2 EMDB-6635, PDB-3jd2: Glutamate dehydrogenase in complex with NADH, open conformation 手法: EM (単粒子) / 解像度: 3.3 Å
化合物	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 ChemComp-NAI*: 1,4-DIHYDRONICOTINAMIDE ADENINE DINUCLEOTIDE / NADH / ニコチンアミドアデニンジヌクレオチド
由来	bos taurus (ウシ) unidentified (未定義)
キーワード	OXIDOREDUCTASE (酸化還元酵素) / glutamate metabolism (グルタミン酸) / mitochondria (ミトコンドリア)