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	Nucleotide- and metalloid-driven conformational changes in the arsenite efflux ATPase ArsA.
ジャーナル・号・ページ	Proc Natl Acad Sci U S A, Vol. 122, Issue 35, Page e2506440122, Year 2025
掲載日	2025年9月2日
著者	Shivansh Mahajan / Ashley E Pall / Yancheng E Li / Timothy L Stemmler / Douglas C Rees / William M Clemons /
PubMed 要旨	Arsenite (As) is toxic to all organisms due to its ability to tightly bind exposed thiols within cells. An important As resistance mechanism in prokaryotes involves proteins encoded by the operon. A ...Arsenite (As) is toxic to all organisms due to its ability to tightly bind exposed thiols within cells. An important As resistance mechanism in prokaryotes involves proteins encoded by the operon. A central component of the operon in many bacteria is the cytoplasmic ATPase, ArsA, which orchestrates a series of nucleotide-dependent handoffs, starting with the capture of As by the ArsD metallochaperone and culminating in its removal from the cell by the ArsB efflux pump. Although the mechanism of ArsA has been widely studied, the molecular details of how nucleotide hydrolysis modulates these events remain unclear. ArsA is an archetypal member of the intradimeric Walker A (IWA) family of ATPases, implicated in a diversity of complex biological functions. Conformational changes typical of IWA ATPases have been postulated to drive these molecular events but have not been demonstrated. We report cryogenic electron microscopy (cryo-EM) structures of ArsA in MgADP-bound and MgATP-bound states, as well as a distinct MgATP-bound state liganded to As. X-ray absorption spectroscopy (XAS) confirmed three-coordinate binding of As to the conserved cysteines at the metalloid-binding site of the closed state. Coupled with biochemical characterization, our cryo-EM structures reveal key conformational changes in the ArsA catalytic cycle consistent with other IWA ATPases and provide the structural basis for allosteric activation of nucleotide hydrolysis by As. This work establishes how the nucleotide state of ArsA transiently creates a high-affinity binding site that can sequester metalloid within the cell, followed by a nucleotide-driven handoff to ArsB for efflux.
リンク	Proc Natl Acad Sci U S A / PubMed:40880530 / PubMed Central
手法	EM (単粒子)
解像度	3.0 - 6.6 Å
構造データ	49231 9nbl EMDB-49231, PDB-9nbl: Open conformation of ArsA from L. ferriphilum in complex with MgADP determined in the presence of arsenite 手法: EM (単粒子) / 解像度: 3.4 Å 49232 9nbm EMDB-49232, PDB-9nbm: Open conformation of ArsA from L. ferriphilum in complex with MgADP determined in absence of arsenite 手法: EM (単粒子) / 解像度: 3.8 Å EMDB-49233: Open conformation of ArsA from L. ferriphilum in presence of MgATP 手法: EM (単粒子) / 解像度: 6.6 Å 49234 9nbo EMDB-49234, PDB-9nbo: Closed conformation of ArsA from L. ferriphilum in complex with MgATP and arsenite 手法: EM (単粒子) / 解像度: 3.0 Å 49237 9nbw EMDB-49237, PDB-9nbw: Closed conformation of ArsA from L. ferriphilum in complex with MgATP and arsenite at 1.5 minute time point 手法: EM (単粒子) / 解像度: 3.0 Å
化合物	ChemComp-ADP: ADENOSINE-5'-DIPHOSPHATE / ADP / ADP, エネルギー貯蔵分子YM ChemComp-MG: Unknown entry / マグネシウムジカチオン ChemComp-ATP: ADENOSINE-5'-TRIPHOSPHATE / ATP / ATP, エネルギー貯蔵分子YM ChemComp-ARS: ARSENIC / アルシン ChemComp-HOH: WATER
由来	leptospirillum ferriphilum (バクテリア) leptospirillum ferriphilum ml-04 (バクテリア)
キーワード	HYDROLASE / ATPase / open conformation / arsenite / arsenic / ADP / Intradimeric Walker A / closed conformation / closed state / ATP