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Structural basis for catalysis and substrate specificity of human ACAT1 期刊论文
NATURE, 2020, 581 (7808) : 333-+
作者:  Jiao, Huipeng;  Wachsmuth, Laurens;  Kumari, Snehlata;  Schwarzer, Robin;  Lin, Juan;  Eren, Remzi Onur;  Fisher, Amanda;  Lane, Rebecca;  Young, George R.;  Kassiotis, George;  Kaiser, William J.;  Pasparakis, Manolis
收藏  |  浏览/下载:10/0  |  提交时间:2020/07/03

The structure of human ACAT1, which catalyses the transfer of an acyl group from acyl-coenzyme A to cholesterol to form cholesteryl ester, is resolved by cryo-electron microscopy.


As members of the membrane-bound O-acyltransferase (MBOAT) enzyme family, acyl-coenzyme A:cholesterol acyltransferases (ACATs) catalyse the transfer of an acyl group from acyl-coenzyme A to cholesterol to generate cholesteryl ester, the primary form in which cholesterol is stored in cells and transported in plasma(1). ACATs have gained attention as potential drug targets for the treatment of diseases such as atherosclerosis, Alzheimer'  s disease and cancer(2-7). Here we present the cryo-electron microscopy structure of human ACAT1 as a dimer of dimers. Each protomer consists of nine transmembrane segments, which enclose a cytosolic tunnel and a transmembrane tunnel that converge at the predicted catalytic site. Evidence from structure-guided mutational analyses suggests that acyl-coenzyme A enters the active site through the cytosolic tunnel, whereas cholesterol may enter from the side through the transmembrane tunnel. This structural and biochemical characterization helps to rationalize the preference of ACAT1 for unsaturated acyl chains, and provides insight into the catalytic mechanism of enzymes within the MBOAT family(8).


  
Frequency-Dependent P Wave Polarization and Its Subwavelength Near-Surface Depth Sensitivity 期刊论文
GEOPHYSICAL RESEARCH LETTERS, 2019
作者:  Park, Sunyoung;  Tsai, Victor C.;  Ishii, Miaki
收藏  |  浏览/下载:8/0  |  提交时间:2020/02/17
body-wave polarization  depth sensitivity  near-surface structure  site characterization  seismic hazard assessment  Japan  
West Valley Demonstration Project Annual Site Environmental Report Calendar Year 2013 科技报告
来源:US Department of Energy (DOE). 出版年: 2014
作者:  Rendall, John D.;  Steiner, Alison F.;  Pendl, Michael P.
收藏  |  浏览/下载:6/0  |  提交时间:2019/04/05
West Valley Demonstration Project  WVDP  Annual Site Environmental Report  ASER  Calendar Year 2013  CH2M HILL • B&W West Valley  LLC  DE-EM0001529  Public Health and Safety and the Environment Are Protected  Airborne and Waterborne Releases to the MEOSI  Climate Change  DOE/NYSERDA Consent Decree  Dose Assessment  Dose to Biota  Drinking Water  Environmental Characterization Support Services  Environmental Compliance  Environmental Management System: EMS  Environmental Monitoring  Groundwater Protection Program  High-Level Waste (HLW) Canister Interim Storage System  HLW canister storage pad  National Emissions Standards for Hazardous Air Pollutants  NESHAP  National Environmental Policy Act  NEPA  North Plateau Full-Scale Permeable Treatment Wall  PTW  Nuclear Regulatory Commission (NRC)-Licensed Disposal Area  NDA  Performance Indicators  Phase 1 Decommissioning and Facility Disposition Contract  Phase 1 Studies  Quality Assurance  Record of Decision  ROD  Resource Conservation and Recovery Act  RCRA  Safety Success  Site Sustainability Plan  SSP  State Pollutant Discharge Elimination System (SPDES) Permit Noncompliance  SPDES  Tank and Vault Drying System  T&VDS  Vertical Storage Casks  VSC  Waste Minimization and Pollution Prevention  Waste Tank Farm  WTF  Waste-Incidental-to-Reprocessing  WIR  
Development of HydroImage, A User Friendly Hydrogeophysical Characterization Software 科技报告
来源:US Department of Energy (DOE). 出版年: 2014
作者:  Mok, Chin Man;  Hubbard, Susan;  Chen, Jinsong;  Suribhatla, Raghu;  Kaback, Dawn Samara
收藏  |  浏览/下载:7/0  |  提交时间:2019/04/05
hydrogeophysical  hydrogeological  software  statistical  characterization  geophysical  parameter estimation  conceptual site model  
West Valley Demonstration Project Annual Site Environmental Report Calendar Year 2010 科技报告
来源:US Department of Energy (DOE). 出版年: 2011
作者:  Johnson, Kenneth I.;  Alvine, Kyle J.;  Skorski, Daniel C.;  Nguyen, Ba Nghiep;  Kafentzis, Tyler A.;  Dahl, Michael E.;  Pitman, Stan G.
收藏  |  浏览/下载:8/0  |  提交时间:2019/04/05
West Valley Demonstration Project  WVDP  Annual Site Environmental Report  ASER  Calendar Year 2010  CH2MHILL • B&W West Valley  LLC  DE-EM0001529  Public Health and Safety & Environmental Protection  Record of Decision  Environmental Characterization a  
Characterization of Microbial Communities in Subsurface Nuclear Blast Cavities of the Nevada Test Site 科技报告
来源:US Department of Energy (DOE). 出版年: 2010
作者:  Moser, Duane P.;  Bruckner, Jim;  Fisher, Jen;  Czerwinski, Ken;  Russell, Charles E.;  Zavarin, Mavrik
收藏  |  浏览/下载:7/0  |  提交时间:2019/04/05
Characterization of Microbial Communities in Subsurface Nuclear Blast Cavities of the Nevada Test Site