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	Architecture and regulation of filamentous human cystathionine beta-synthase.
ジャーナル・号・ページ	Nat Commun, Vol. 15, Issue 1, Page 2931, Year 2024
掲載日	2024年4月4日
著者	Thomas J McCorvie / Douglas Adamoski / Raquel A C Machado / Jiazhi Tang / Henry J Bailey / Douglas S M Ferreira / Claire Strain-Damerell / Arnaud Baslé / Andre L B Ambrosio / Sandra M G Dias / Wyatt W Yue /
PubMed 要旨	Cystathionine beta-synthase (CBS) is an essential metabolic enzyme across all domains of life for the production of glutathione, cysteine, and hydrogen sulfide. Appended to the conserved catalytic ...Cystathionine beta-synthase (CBS) is an essential metabolic enzyme across all domains of life for the production of glutathione, cysteine, and hydrogen sulfide. Appended to the conserved catalytic domain of human CBS is a regulatory domain that modulates activity by S-adenosyl-L-methionine (SAM) and promotes oligomerisation. Here we show using cryo-electron microscopy that full-length human CBS in the basal and SAM-bound activated states polymerises as filaments mediated by a conserved regulatory domain loop. In the basal state, CBS regulatory domains sterically block the catalytic domain active site, resulting in a low-activity filament with three CBS dimers per turn. This steric block is removed when in the activated state, one SAM molecule binds to the regulatory domain, forming a high-activity filament with two CBS dimers per turn. These large conformational changes result in a central filament of SAM-stabilised regulatory domains at the core, decorated with highly flexible catalytic domains. Polymerisation stabilises CBS and reduces thermal denaturation. In PC-3 cells, we observed nutrient-responsive CBS filamentation that disassembles when methionine is depleted and reversed in the presence of SAM. Together our findings extend our understanding of CBS enzyme regulation, and open new avenues for investigating the pathogenic mechanism and therapeutic opportunities for CBS-associated disorders.
リンク	Nat Commun / PubMed:38575566 / PubMed Central
手法	EM (らせん対称) / EM (単粒子)
解像度	3.1 - 4.1 Å
構造データ	19735 8s5h EMDB-19735, PDB-8s5h: Full-length human cystathionine beta-synthase with C-terminal 6xHis-tag, basal state, helical reconstruction 手法: EM (らせん対称) / 解像度: 3.7 Å 19736 8s5i EMDB-19736, PDB-8s5i: Full-length human cystathionine beta-synthase with C-terminal 6xHis-tag, basal state, single particle reconstruction 手法: EM (単粒子) / 解像度: 3.1 Å 19737 8s5j EMDB-19737, PDB-8s5j: Full-length human cystathionine beta-synthase, basal state, helical reconstruction 手法: EM (らせん対称) / 解像度: 3.9 Å 19738 8s5k EMDB-19738, PDB-8s5k: Full-length human cystathionine beta-synthase, basal state, single particle reconstruction 手法: EM (単粒子) / 解像度: 3.8 Å 19739 8s5l EMDB-19739, PDB-8s5l: Full-length human cystathionine beta-synthase, basal state, partially degraded tetramer 手法: EM (単粒子) / 解像度: 3.8 Å 19740 8s5m EMDB-19740, PDB-8s5m: Full-length human cystathionine beta-synthase with C-terminal 6xHis-tag, SAM bound, activated state, helical reconstruction 手法: EM (らせん対称) / 解像度: 4.0 Å EMDB-19741: Full-length human cystathionine beta-synthase with C-terminal 6xHis-tag, SAM bound, activated state, local helical reconstruction 手法: EM (らせん対称) / 解像度: 4.1 Å EMDB-19742: Full-length human cystathionine beta-synthase with C-terminal 6xHis-tag, SAM bound, activated state, local single particle reconstruction 手法: EM (単粒子) / 解像度: 4.1 Å
化合物	ChemComp-HEM: PROTOPORPHYRIN IX CONTAINING FE ChemComp-PLP: PYRIDOXAL-5'-PHOSPHATE / ピリドキサ-ル5′-りん酸 ChemComp-SAM: S-ADENOSYLMETHIONINE
由来	homo sapiens (ヒト)
キーワード	TRANSFERASE / Filament / Allostery