[English] 日本語
Yorodumi
- EMDB-24208: Structure of PPPA bound human ACAT2 -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: EMDB / ID: EMD-24208
TitleStructure of PPPA bound human ACAT2
Map data
Samplehuman ACAT2 with PPPA:
Sterol O-acyltransferase 2 / (ligand) x 3
Function / homology
Function and homology information


sterol O-acyltransferase / sterol O-acyltransferase activity / cholesterol O-acyltransferase activity / cholesterol esterification / O-acyltransferase activity / very-low-density lipoprotein particle assembly / intestinal cholesterol absorption / fatty-acyl-CoA binding / LDL clearance / low-density lipoprotein particle clearance ...sterol O-acyltransferase / sterol O-acyltransferase activity / cholesterol O-acyltransferase activity / cholesterol esterification / O-acyltransferase activity / very-low-density lipoprotein particle assembly / intestinal cholesterol absorption / fatty-acyl-CoA binding / LDL clearance / low-density lipoprotein particle clearance / cholesterol efflux / cholesterol binding / macrophage derived foam cell differentiation / acyltransferase activity / brush border / cholesterol homeostasis / cholesterol metabolic process / endoplasmic reticulum membrane / endoplasmic reticulum / integral component of membrane
Similarity search - Function
Sterol O-acyltransferase, metazoa / Sterol O-acyltransferase, ACAT/DAG/ARE types / MBOAT, membrane-bound O-acyltransferase family / Membrane bound O-acyl transferase, MBOAT
Similarity search - Domain/homology
Sterol O-acyltransferase 2
Similarity search - Component
Biological speciesHomo sapiens (human)
Methodsingle particle reconstruction / cryo EM / Resolution: 3.87 Å
AuthorsLi X / Long T
Funding support1 items
OrganizationGrant numberCountry
Not funded
CitationJournal: Structure / Year: 2021
Title: Molecular structures of human ACAT2 disclose mechanism for selective inhibition.
Authors: Tao Long / Yang Liu / Xiaochun Li /
Abstract: Endoplasmic reticulum-localized acyl-CoA:cholesterol acyltransferases (ACAT), including ACAT1 and ACAT2, convert cholesterol to cholesteryl esters that become incorporated into lipoproteins or stored ...Endoplasmic reticulum-localized acyl-CoA:cholesterol acyltransferases (ACAT), including ACAT1 and ACAT2, convert cholesterol to cholesteryl esters that become incorporated into lipoproteins or stored in cytosolic lipid droplets. Selective inhibition of ACAT2 has been shown to considerably attenuate hypercholesterolemia and atherosclerosis in mice. Here, we report cryogenic electron microscopy structures of human ACAT2 bound to its specific inhibitor pyripyropene A or the general ACAT inhibitor nevanimibe. Structural analysis reveals that ACAT2 has a topology in membranes similar to that of ACAT1. A catalytic core with an entry site occupied by a cholesterol molecule and another site for allosteric activation of ACAT2 is observed in these structures. Enzymatic assays show that mutations within sites of cholesterol entry or allosteric activation attenuate ACAT2 activity in vitro. Together, these results reveal mechanisms for ACAT2-mediated esterification of cholesterol, providing a blueprint to design new ACAT2 inhibitors for use in the prevention of cardiovascular disease.
History
DepositionJun 8, 2021-
Header (metadata) releaseSep 22, 2021-
Map releaseSep 22, 2021-
UpdateSep 22, 2021-
Current statusSep 22, 2021Processing site: RCSB / Status: Released

-
Structure visualization

Movie
  • Surface view with section colored by density value
  • Surface level: 6
  • Imaged by UCSF Chimera
  • Download
  • Surface view colored by cylindrical radius
  • Surface level: 6
  • Imaged by UCSF Chimera
  • Download
  • Surface view with fitted model
  • Atomic models: PDB-7n6q
  • Surface level: 6
  • Imaged by UCSF Chimera
  • Download
Movie viewer
Structure viewerEM map:
SurfViewMolmilJmol/JSmol
Supplemental images

Downloads & links

-
Map

FileDownload / File: emd_24208.map.gz / Format: CCP4 / Size: 137.1 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Projections & slices

Image control

Size
Brightness
Contrast
Others
AxesX (Sec.)Y (Row.)Z (Col.)
0.83 Å/pix.
x 330 pix.
= 274.89 Å
0.83 Å/pix.
x 330 pix.
= 274.89 Å
0.83 Å/pix.
x 330 pix.
= 274.89 Å

Surface

Projections

Slices (1/3)

Slices (1/2)

Slices (2/3)

Images are generated by Spider.

Voxel sizeX=Y=Z: 0.833 Å
Density
Contour LevelBy AUTHOR: 6.0 / Movie #1: 6
Minimum - Maximum-25.685274 - 42.70983
Average (Standard dev.)-0.0053105624 (±1.0248835)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderZYX
Origin000
Dimensions330330330
Spacing330330330
CellA=B=C: 274.89 Å
α=β=γ: 90.0 °

CCP4 map header:

modeImage stored as Reals
Å/pix. X/Y/Z0.8330.8330.833
M x/y/z330330330
origin x/y/z0.0000.0000.000
length x/y/z274.890274.890274.890
α/β/γ90.00090.00090.000
start NX/NY/NZ000
NX/NY/NZ330330330
MAP C/R/S321
start NC/NR/NS000
NC/NR/NS330330330
D min/max/mean-25.68542.710-0.005

-
Supplemental data

-
Sample components

+
Entire human ACAT2 with PPPA

EntireName: human ACAT2 with PPPA / Number of Components: 5

+
Component #1: cellular-component, human ACAT2 with PPPA

Cellular-componentName: human ACAT2 with PPPA / Recombinant expression: No
SourceSpecies: Homo sapiens (human)
Source (engineered)Expression System: Homo sapiens (human)

+
Component #2: protein, Sterol O-acyltransferase 2

ProteinName: Sterol O-acyltransferase 2 / Number of Copies: 4 / Recombinant expression: No
MassTheoretical: 60.893 kDa
SourceSpecies: Homo sapiens (human)
Source (engineered)Expression System: Homo sapiens (human)

+
Component #3: ligand, (3S,4R,4aR,6S,6aS,12R,12aS,12bS)-4-[(acetyloxy)methyl]-12...

LigandName: (3S,4R,4aR,6S,6aS,12R,12aS,12bS)-4-[(acetyloxy)methyl]-12-hydroxy-4,6a,12b-trimethyl-11-oxo-9-(pyridin-3-yl)-1,3,4,4a,5,6,6a,12,12a,12b-decahydro-2H,11H-naphtho[2,1-b]pyrano[3,4-e]pyran-3,6-diyl diacetate
Number of Copies: 4 / Recombinant expression: No
MassTheoretical: 0.583626 kDa

+
Component #4: ligand, CHOLESTEROL

LigandName: CHOLESTEROL / Number of Copies: 8 / Recombinant expression: No
MassTheoretical: 0.386654 kDa

+
Component #5: ligand, OLEIC ACID

LigandName: OLEIC ACID / Number of Copies: 4 / Recombinant expression: No
MassTheoretical: 0.282461 kDa

-
Experimental details

-
Sample preparation

SpecimenSpecimen State: Particle / Method: cryo EM
Sample solutionpH: 7.5
VitrificationCryogen Name: ETHANE

-
Electron microscopy imaging

Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company
ImagingMicroscope: FEI TITAN KRIOS
Electron gunElectron Source: FIELD EMISSION GUN / Accelerating Voltage: 300 kV / Electron Dose: 60 e/Å2 / Illumination Mode: FLOOD BEAM
LensImaging Mode: DARK FIELD
Specimen HolderModel: OTHER
CameraDetector: OTHER

-
Image processing

ProcessingMethod: single particle reconstruction / Number of Projections: 153208
3D reconstructionResolution: 3.87 Å / Resolution Method: FSC 0.143 CUT-OFF

-
Atomic model buiding

Output model

+
About Yorodumi

-
News

-
Aug 12, 2020. Covid-19 info

Covid-19 info

URL: https://pdbj.org/emnavi/covid19.php

New page: Covid-19 featured information page in EM Navigator.

Related info.:Covid-19 info / Mar 5, 2020. Novel coronavirus structure data

-
Mar 5, 2020. Novel coronavirus structure data

Novel coronavirus structure data

Related info.:Yorodumi Speices / Aug 12, 2020. Covid-19 info

External links:COVID-19 featured content - PDBj / Molecule of the Month (242):Coronavirus Proteases

+
Jan 31, 2019. EMDB accession codes are about to change! (news from PDBe EMDB page)

EMDB accession codes are about to change! (news from PDBe EMDB page)

  • The allocation of 4 digits for EMDB accession codes will soon come to an end. Whilst these codes will remain in use, new EMDB accession codes will include an additional digit and will expand incrementally as the available range of codes is exhausted. The current 4-digit format prefixed with “EMD-” (i.e. EMD-XXXX) will advance to a 5-digit format (i.e. EMD-XXXXX), and so on. It is currently estimated that the 4-digit codes will be depleted around Spring 2019, at which point the 5-digit format will come into force.
  • The EM Navigator/Yorodumi systems omit the EMD- prefix.

Related info.:Q: What is EMD? / ID/Accession-code notation in Yorodumi/EM Navigator

External links:EMDB Accession Codes are Changing Soon! / Contact to PDBj

+
Jul 12, 2017. Major update of PDB

Major update of PDB

  • wwPDB released updated PDB data conforming to the new PDBx/mmCIF dictionary.
  • This is a major update changing the version number from 4 to 5, and with Remediation, in which all the entries are updated.
  • In this update, many items about electron microscopy experimental information are reorganized (e.g. em_software).
  • Now, EM Navigator and Yorodumi are based on the updated data.

External links:wwPDB Remediation / Enriched Model Files Conforming to OneDep Data Standards Now Available in the PDB FTP Archive

+
Jun 16, 2017. Omokage search with filter

Omokage search with filter

Result of Omokage search can be filtered by keywords and the database types

Related info.:Omokage search

-
Yorodumi

Thousand views of thousand structures

  • Yorodumi is a browser for structure data from EMDB, PDB, SASBDB, etc.
  • This page is also the successor to EM Navigator detail page, and also detail information page/front-end page for Omokage search.
  • The word "yorodu" (or yorozu) is an old Japanese word meaning "ten thousand". "mi" (miru) is to see.

Related info.:EMDB / PDB / SASBDB / Comparison of 3 databanks / Yorodumi Search / Aug 31, 2016. New EM Navigator & Yorodumi / Yorodumi Papers / Jmol/JSmol / Function and homology information / Changes in new EM Navigator and Yorodumi

Read more