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- EMDB-0832: Structure of the human sterol O-acyltransferase 1 in resting state -
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Open data
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Basic information
Entry | Database: EMDB / ID: EMD-0832 | ||||||||||||||||||
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Title | Structure of the human sterol O-acyltransferase 1 in resting state | ||||||||||||||||||
![]() | postprocessed map from relion | ||||||||||||||||||
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![]() | SOAT / ACAT / MBOAT / MEMBRANE PROTEIN / TRANSFERASE | ||||||||||||||||||
Function / homology | ![]() sterol O-acyltransferase / sterol O-acyltransferase activity / cholesterol O-acyltransferase activity / cholesterol storage / positive regulation of amyloid precursor protein biosynthetic process / very-low-density lipoprotein particle assembly / low-density lipoprotein particle clearance / fatty-acyl-CoA binding / LDL clearance / cholesterol efflux ...sterol O-acyltransferase / sterol O-acyltransferase activity / cholesterol O-acyltransferase activity / cholesterol storage / positive regulation of amyloid precursor protein biosynthetic process / very-low-density lipoprotein particle assembly / low-density lipoprotein particle clearance / fatty-acyl-CoA binding / LDL clearance / cholesterol efflux / macrophage derived foam cell differentiation / cholesterol binding / cholesterol metabolic process / cholesterol homeostasis / endoplasmic reticulum membrane / endoplasmic reticulum / membrane / identical protein binding Similarity search - Function | ||||||||||||||||||
Biological species | ![]() | ||||||||||||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.5 Å | ||||||||||||||||||
![]() | Chen L / Guan C | ||||||||||||||||||
Funding support | ![]()
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![]() | ![]() Title: Structural insights into the inhibition mechanism of human sterol O-acyltransferase 1 by a competitive inhibitor. Authors: Chengcheng Guan / Yange Niu / Si-Cong Chen / Yunlu Kang / Jing-Xiang Wu / Koji Nishi / Catherine C Y Chang / Ta-Yuan Chang / Tuoping Luo / Lei Chen / ![]() ![]() Abstract: Sterol O-acyltransferase 1 (SOAT1) is an endoplasmic reticulum (ER) resident, multi-transmembrane enzyme that belongs to the membrane-bound O-acyltransferase (MBOAT) family. It catalyzes the ...Sterol O-acyltransferase 1 (SOAT1) is an endoplasmic reticulum (ER) resident, multi-transmembrane enzyme that belongs to the membrane-bound O-acyltransferase (MBOAT) family. It catalyzes the esterification of cholesterol to generate cholesteryl esters for cholesterol storage. SOAT1 is a target to treat several human diseases. However, its structure and mechanism remain elusive since its discovery. Here, we report the structure of human SOAT1 (hSOAT1) determined by cryo-EM. hSOAT1 is a tetramer consisted of a dimer of dimer. The structure of hSOAT1 dimer at 3.5 Å resolution reveals that a small molecule inhibitor CI-976 binds inside the catalytic chamber and blocks the accessibility of the active site residues H460, N421 and W420. Our results pave the way for future mechanistic study and rational drug design targeting hSOAT1 and other mammalian MBOAT family members. | ||||||||||||||||||
History |
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Structure visualization
Movie |
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Structure viewer | EM map: ![]() ![]() ![]() |
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 2.7 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 10.9 KB 10.9 KB | Display Display | ![]() |
FSC (resolution estimation) | ![]() | 7.2 KB | Display | ![]() |
Images | ![]() | 265.3 KB | ||
Filedesc metadata | ![]() | 5.3 KB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Validation report
Summary document | ![]() | 386 KB | Display | ![]() |
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Full document | ![]() | 385.6 KB | Display | |
Data in XML | ![]() | 9.5 KB | Display | |
Data in CIF | ![]() | 12.3 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 6l48MC ![]() 0829C ![]() 0830C ![]() 0831C ![]() 6l47C M: atomic model generated by this map C: citing same article ( |
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Similar structure data |
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Links
EMDB pages | ![]() ![]() |
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Related items in Molecule of the Month |
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Map
File | ![]() | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Annotation | postprocessed map from relion | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 1.045 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
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Sample components
-Entire : human sterol O-acyltransferase 1 dimer
Entire | Name: human sterol O-acyltransferase 1 dimer |
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Components |
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-Supramolecule #1: human sterol O-acyltransferase 1 dimer
Supramolecule | Name: human sterol O-acyltransferase 1 dimer / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1 |
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Source (natural) | Organism: ![]() |
-Macromolecule #1: Sterol O-acyltransferase 1
Macromolecule | Name: Sterol O-acyltransferase 1 / type: protein_or_peptide / ID: 1 / Number of copies: 2 / Enantiomer: LEVO / EC number: sterol O-acyltransferase |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 57.294777 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: MKEVGSHFDD FVTNLIEKSA SLDNGGCALT TFSVLEGEKN NHRAKDLRAP PEQGKIFIAR RSLLDELLEV DHIRTIYHMF IALLILFIL STLVVDYIDE GRLVLEFSLL SYAFGKFPTV VWTWWIMFLS TFSVPYFLFQ HWATGYSKSS HPLIRSLFHG F LFMIFQIG ...String: MKEVGSHFDD FVTNLIEKSA SLDNGGCALT TFSVLEGEKN NHRAKDLRAP PEQGKIFIAR RSLLDELLEV DHIRTIYHMF IALLILFIL STLVVDYIDE GRLVLEFSLL SYAFGKFPTV VWTWWIMFLS TFSVPYFLFQ HWATGYSKSS HPLIRSLFHG F LFMIFQIG VLGFGPTYVV LAYTLPPASR FIIIFEQIRF VMKAHSFVRE NVPRVLNSAK EKSSTVPIPT VNQYLYFLFA PT LIYRDSY PRNPTVRWGY VAMKFAQVFG CFFYVYYIFE RLCAPLFRNI KQEPFSARVL VLCVFNSILP GVLILFLTFF AFL HCWLNA FAEMLRFGDR MFYKDWWNST SYSNYYRTWN VVVHDWLYYY AYKDFLWFFS KRFKSAAMLA VFAVSAVVHE YALA VCLSF FYPVLFVLFM FFGMAFNFIV NDSRKKPIWN VLMWTSLFLG NGVLLCFYSQ EWYARQHCPL KNPTFLDYVR PRSWT CRYV F UniProtKB: Sterol O-acyltransferase 1 |
-Macromolecule #2: CHOLESTEROL
Macromolecule | Name: CHOLESTEROL / type: ligand / ID: 2 / Number of copies: 2 / Formula: CLR |
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Molecular weight | Theoretical: 386.654 Da |
Chemical component information | ![]() ChemComp-CLR: |
-Experimental details
-Structure determination
Method | cryo EM |
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![]() | single particle reconstruction |
Aggregation state | particle |
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Sample preparation
Buffer | pH: 7.5 |
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Vitrification | Cryogen name: ETHANE |
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Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K2 QUANTUM (4k x 4k) / Average electron dose: 50.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |