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	High-resolution structures of the SAMHD1 dGTPase homolog from Leeuwenhoekiella blandensis reveal a novel mechanism of allosteric activation by dATP.
ジャーナル・号・ページ	J Biol Chem, Vol. 298, Issue 7, Page 102073, Year 2022
掲載日	2022年5月26日
著者	Bradley P Klemm / Andrew P Sikkema / Allen L Hsu / James C Horng / Traci M Tanaka Hall / Mario J Borgnia / Roel M Schaaper /
PubMed 要旨	Deoxynucleoside triphosphate (dNTP) triphosphohydrolases (dNTPases) are important enzymes that may perform multiple functions in the cell, including regulating the dNTP pools and contributing to ...Deoxynucleoside triphosphate (dNTP) triphosphohydrolases (dNTPases) are important enzymes that may perform multiple functions in the cell, including regulating the dNTP pools and contributing to innate immunity against viruses. Among the homologs that are best studied are human sterile alpha motif and HD domain-containing protein 1 (SAMHD1), a tetrameric dNTPase, and the hexameric Escherichia coli dGTPase; however, it is unclear whether these are representative of all dNTPases given their wide distribution throughout life. Here, we investigated a hexameric homolog from the marine bacterium Leeuwenhoekiella blandensis, revealing that it is a dGTPase that is subject to allosteric activation by dATP, specifically. Allosteric regulation mediated solely by dATP represents a novel regulatory feature among dNTPases that may facilitate maintenance of cellular dNTP pools in L. blandensis. We present high-resolution X-ray crystallographic structures (1.80-2.26 Å) in catalytically important conformations as well as cryo-EM structures (2.1-2.7 Å) of the enzyme bound to dGTP and dATP ligands. The structures, the highest resolution cryo-EM structures of any SAMHD1-like dNTPase to date, reveal an intact metal-binding site with the dGTP substrate coordinated to three metal ions. These structural and biochemical data yield insights into the catalytic mechanism and support a conserved catalytic mechanism for the tetrameric and hexameric dNTPase homologs. We conclude that the allosteric activation by dATP appears to rely on structural connectivity between the allosteric and active sites, as opposed to the changes in oligomeric state upon ligand binding used by SAMHD1.
リンク	J Biol Chem / PubMed:35643313 / PubMed Central
手法	EM (単粒子) / X線回折
解像度	1.8 - 2.7 Å
構造データ	26126 7tu5 EMDB-26126, PDB-7tu5: Structure of the L. blandensis dGTPase in the apo form 手法: EM (単粒子) / 解像度: 2.1 Å 26127 7tu6 EMDB-26127, PDB-7tu6: Structure of the L. blandensis dGTPase bound to dATP 手法: EM (単粒子) / 解像度: 2.7 Å 26128 7tu7 EMDB-26128, PDB-7tu7: Structure of the L. blandensis dGTPase H125A mutant bound to dGTP 手法: EM (単粒子) / 解像度: 2.5 Å 26129 7tu8 EMDB-26129, PDB-7tu8: Structure of the L. blandensis dGTPase H125A mutant bound to dGTP and dATP 手法: EM (単粒子) / 解像度: 2.6 Å PDB-7tu0: Structure of the L. blandensis dGTPase bound to Mn 手法: X-RAY DIFFRACTION / 解像度: 2.04 Å PDB-7tu1: Structure of the L. blandensis dGTPase R37A mutant 手法: X-RAY DIFFRACTION / 解像度: 1.8 Å PDB-7tu2: Structure of the L. blandensis dGTPase R37A mutant bound to Mn 手法: X-RAY DIFFRACTION / 解像度: 2.13 Å PDB-7tu3: Structure of the L. blandensis dGTPase del55-58 mutant 手法: X-RAY DIFFRACTION / 解像度: 2.17 Å PDB-7tu4: Structure of the L. blandensis dGTPase del55-58 mutant bound to Mn 手法: X-RAY DIFFRACTION / 解像度: 2.26 Å
化合物	ChemComp-SO4: SULFATE ION / 硫酸ジアニオン ChemComp-MN: Unknown entry ChemComp-HOH: WATER ChemComp-EDO: 1,2-ETHANEDIOL / エチレングリコ-ル ChemComp-MG: Unknown entry / マグネシウムジカチオン ChemComp-DTP: 2'-DEOXYADENOSINE 5'-TRIPHOSPHATE / dATP ChemComp-DGT: 2'-DEOXYGUANOSINE-5'-TRIPHOSPHATE / dGTP
由来	leeuwenhoekiella blandensis med217 (バクテリア) leeuwenhoekiella blandensis (バクテリア)
キーワード	HYDROLASE / dGTPase / nucleotide binding