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Structure paper

タイトル	Human CTP synthase filament structure reveals the active enzyme conformation.
ジャーナル・号・ページ	Nat Struct Mol Biol, Vol. 24, Issue 6, Page 507-514, Year 2017
掲載日	2017年5月1日
著者	Eric M Lynch / Derrick R Hicks / Matthew Shepherd / James A Endrizzi / Allison Maker / Jesse M Hansen / Rachael M Barry / Zemer Gitai / Enoch P Baldwin / Justin M Kollman /
PubMed 要旨	The universally conserved enzyme CTP synthase (CTPS) forms filaments in bacteria and eukaryotes. In bacteria, polymerization inhibits CTPS activity and is required for nucleotide homeostasis. Here we ...The universally conserved enzyme CTP synthase (CTPS) forms filaments in bacteria and eukaryotes. In bacteria, polymerization inhibits CTPS activity and is required for nucleotide homeostasis. Here we show that for human CTPS, polymerization increases catalytic activity. The cryo-EM structures of bacterial and human CTPS filaments differ considerably in overall architecture and in the conformation of the CTPS protomer, explaining the divergent consequences of polymerization on activity. The structure of human CTPS filament, the first structure of the full-length human enzyme, reveals a novel active conformation. The filament structures elucidate allosteric mechanisms of assembly and regulation that rely on a conserved conformational equilibrium. The findings may provide a mechanism for increasing human CTPS activity in response to metabolic state and challenge the assumption that metabolic filaments are generally storage forms of inactive enzymes. Allosteric regulation of CTPS polymerization by ligands likely represents a fundamental mechanism underlying assembly of other metabolic filaments.
リンク	Nat Struct Mol Biol / PubMed:28459447 / PubMed Central
手法	EM (らせん対称) / EM (単粒子) / X線回折
解像度	2.7 - 17.0 Å
構造データ	8474 5u03 EMDB-8474, PDB-5u03: Cryo-EM structure of the human CTP synthase filament 手法: EM (らせん対称) / 解像度: 6.1 Å 8475 5u05 EMDB-8475, PDB-5u05: Cryo-EM structure of the E. coli CTP synthase tetramer 手法: EM (単粒子) / 解像度: 7.9 Å EMDB-8476: human CTP synthase 1 - mutant H355A 手法: EM (単粒子) / 解像度: 17.0 Å EMDB-8490: E. coli CTP synthase CC mutant filament 手法: EM (らせん対称) / 解像度: 7.6 Å EMDB-8491: E. coli CTP synthase CC mutant filament 手法: EM (らせん対称) / 解像度: 8.6 Å 8504 5u3c EMDB-8504, PDB-5u3c: CryoEM structure of the CTP synthase filament at 4.6 Angstrom resolution 手法: EM (らせん対称) / 解像度: 4.6 Å 8513 5u6r EMDB-8513, PDB-5u6r: E. coli CTP synthase CC mutant filament (product-bound) 手法: EM (らせん対称) / 解像度: 5.7 Å PDB-5tkv: X-RAY CRYSTAL STRUCTURE OF THE "CLOSED" CONFORMATION OF CTP-INHIBITED E. COLI CYTIDINE TRIPHOSPHATE (CTP) SYNTHETASE 手法: X-RAY DIFFRACTION / 解像度: 2.7 Å
化合物	ChemComp-GLN: GLUTAMINE / グルタミン / グルタミン ChemComp-SO4: SULFATE ION / 硫酸ジアニオン / 硫酸塩 ChemComp-MPD: (4S)-2-METHYL-2,4-PENTANEDIOL / (S)-2-メチル-2,4-ペンタンジオ-ル / 沈殿剤YM / 2-Methyl-2,4-pentanediol ChemComp-MG: Unknown entry / マグネシウムジカチオン ChemComp-CTP: CYTIDINE-5'-TRIPHOSPHATE / CTP / シチジン三リン酸 ChemComp-MRD: (4R)-2-METHYLPENTANE-2,4-DIOL / (4R)-2-メチル-2,4-ペンタンジオ-ル / 沈殿剤YM / 2-Methyl-2,4-pentanediol ChemComp-HOH: WATER / 水 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-UTP: URIDINE 5'-TRIPHOSPHATE / UTP / UTPYM / ウリジン三リン酸 ChemComp-ADP: ADENOSINE-5'-DIPHOSPHATE / ADP / ADP, エネルギー貯蔵分子*YM / アデノシン二リン酸
由来	homo sapiens (ヒト) escherichia coli (大腸菌) escherichia coli (strain k12) (大腸菌)
キーワード	LYASE (リアーゼ) / PYRIMIDINE BIOSYNTHESIS / ENZYME REGULATION VIA POLYMERIZATION / FEEDBACK INHIBITION (酵素阻害剤) / LIGASE (リガーゼ) / PROTEIN FIBRIL / nucleotide metabolism (ヌクレオチド) / enzyme (酵素) / filament / active / metabolic filament