[English] 日本語
Yorodumi
- EMDB-35948: Human neutral shpingomyelinase -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: EMDB / ID: EMD-35948
TitleHuman neutral shpingomyelinase
Map data
Sample
  • Complex: human neutral sphingomyelinases
    • Protein or peptide: Sphingomyelin phosphodiesterase 2
  • Ligand: MAGNESIUM ION
  • Ligand: HEPTANE
  • Ligand: TETRADECANE
Keywordsenzyme / membrane protein
Function / homology
Function and homology information


sphingomyelin metabolic process / sphingomyelin catabolic process / Ceramide signalling / sphingomyelin phosphodiesterase / sphingomyelin phosphodiesterase activity / Glycosphingolipid catabolism / ceramide biosynthetic process / phosphoric diester hydrolase activity / sphingolipid catabolic process / TNFR1-mediated ceramide production ...sphingomyelin metabolic process / sphingomyelin catabolic process / Ceramide signalling / sphingomyelin phosphodiesterase / sphingomyelin phosphodiesterase activity / Glycosphingolipid catabolism / ceramide biosynthetic process / phosphoric diester hydrolase activity / sphingolipid catabolic process / TNFR1-mediated ceramide production / response to mechanical stimulus / cell periphery / caveola / intracellular signal transduction / endoplasmic reticulum / metal ion binding / plasma membrane
Similarity search - Function
Sphingomyelin phosphodiesterase 2-like / Endonuclease/exonuclease/phosphatase / Endonuclease/Exonuclease/phosphatase family / Endonuclease/exonuclease/phosphatase superfamily
Similarity search - Domain/homology
Sphingomyelin phosphodiesterase 2
Similarity search - Component
Biological speciesHomo sapiens (human)
Methodsingle particle reconstruction / cryo EM / Resolution: 3.07 Å
AuthorsZhang SS
Funding support China, 1 items
OrganizationGrant numberCountry
National Natural Science Foundation of China (NSFC)32030056 China
CitationJournal: Nat Commun / Year: 2023
Title: Molecular basis for the catalytic mechanism of human neutral sphingomyelinases 1 (hSMPD2).
Authors: Jingbo Yi / Boya Qi / Jian Yin / Ruochong Li / Xudong Chen / Junhan Hu / Guohui Li / Sensen Zhang / Yuebin Zhang / Maojun Yang /
Abstract: Enzymatic breakdown of sphingomyelin by sphingomyelinase (SMase) is the main source of the membrane lipids, ceramides, which are involved in many cellular physiological processes. However, the full- ...Enzymatic breakdown of sphingomyelin by sphingomyelinase (SMase) is the main source of the membrane lipids, ceramides, which are involved in many cellular physiological processes. However, the full-length structure of human neutral SMase has not been resolved; therefore, its catalytic mechanism remains unknown. Here, we resolve the structure of human full-length neutral SMase, sphingomyelinase 1 (SMPD2), which reveals that C-terminal transmembrane helices contribute to dimeric architecture of hSMPD2 and that D111 - K116 loop domain is essential for substrate hydrolysis. Coupled with molecular docking, we clarify the binding pose of sphingomyelin, and site-directed mutagenesis further confirms key residues responsible for sphingomyelin binding. Hybrid quantum mechanics/molecular mechanics (QM/MM) molecular dynamic (MD) simulations are utilized to elaborate the catalysis of hSMPD2 with the reported in vitro substrates, sphingomyelin and lyso-platelet activating fator (lyso-PAF). Our study provides mechanistic details that enhance our knowledge of lipid metabolism and may lead to an improved understanding of ceramide in disease and in cancer treatment.
History
DepositionApr 14, 2023-
Header (metadata) releaseDec 6, 2023-
Map releaseDec 6, 2023-
UpdateMay 1, 2024-
Current statusMay 1, 2024Processing site: PDBc / Status: Released

-
Structure visualization

Supplemental images

emd_35948.png

Downloads & links

-
Map

FileDownload / File: emd_35948.map.gz / Format: CCP4 / Size: 42.9 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Projections & slices

Image control

Size
Brightness
Contrast
Others
AxesZ (Sec.)Y (Row.)X (Col.)
0.84 Å/pix.
x 224 pix.
= 187.578 Å		0.84 Å/pix.
x 224 pix.
= 187.578 Å		0.84 Å/pix.
x 224 pix.
= 187.578 Å

Surface

Projections

Slices (1/3)

Slices (1/2)

Slices (2/3)

Images are generated by Spider.

Voxel sizeX=Y=Z: 0.8374 Å
Density

Histogram

Histogram (log scale)
Contour LevelBy AUTHOR: 0.0169
Minimum - Maximum-0.0784279 - 0.12921256
Average (Standard dev.)0.00023703527 (±0.0037429759)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions224224224
Spacing224224224
CellA=B=C: 187.5776 Å
α=β=γ: 90.0 °

-
Supplemental data

-
Half map: #1

Fileemd_35948_half_map_1.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

-
Half map: #2

Fileemd_35948_half_map_2.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

-
Sample components

-
Entire : human neutral sphingomyelinases

EntireName: human neutral sphingomyelinases
Components
  • Complex: human neutral sphingomyelinases
    • Protein or peptide: Sphingomyelin phosphodiesterase 2
  • Ligand: MAGNESIUM ION
  • Ligand: HEPTANE
  • Ligand: TETRADECANE

-
Supramolecule #1: human neutral sphingomyelinases

SupramoleculeName: human neutral sphingomyelinases / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1
Source (natural)Organism: Homo sapiens (human)

-
Macromolecule #1: Sphingomyelin phosphodiesterase 2

MacromoleculeName: Sphingomyelin phosphodiesterase 2 / type: protein_or_peptide / ID: 1 / Number of copies: 2 / Enantiomer: LEVO / EC number: sphingomyelin phosphodiesterase
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 47.702508 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: MKPNFSLRLR IFNLNCWGIP YLSKHRADRM RRLGDFLNQE SFDLALLEEV WSEQDFQYLR QKLSPTYPAA HHFRSGIIGS GLCVFSKHP IQELTQHIYT LNGYPYMIHH GDWFSGKAVG LLVLHLSGMV LNAYVTHLHA EYNRQKDIYL AHRVAQAWEL A QFIHHTSK ...String:
MKPNFSLRLR IFNLNCWGIP YLSKHRADRM RRLGDFLNQE SFDLALLEEV WSEQDFQYLR QKLSPTYPAA HHFRSGIIGS GLCVFSKHP IQELTQHIYT LNGYPYMIHH GDWFSGKAVG LLVLHLSGMV LNAYVTHLHA EYNRQKDIYL AHRVAQAWEL A QFIHHTSK KADVVLLCGD LNMHPEDLGC CLLKEWTGLH DAYLETRDFK GSEEGNTMVP KNCYVSQQEL KPFPFGVRID YV LYKAVSG FYISCKSFET TTGFDPHRGT PLSDHEALMA TLFVRHSPPQ QNPSSTHGPA ERSPLMCVLK EAWTELGLGM AQA RWWATF ASYVIGLGLL LLALLCVLAA GGGAGEAAIL LWTPSVGLVL WAGAFYLFHV QEVNGLYRAQ AELQHVLGRA REAQ DLGPE PQPALLLGQQ EGDRTKEQ

UniProtKB: Sphingomyelin phosphodiesterase 2

-
Macromolecule #2: MAGNESIUM ION

MacromoleculeName: MAGNESIUM ION / type: ligand / ID: 2 / Number of copies: 2 / Formula: MG
Molecular weightTheoretical: 24.305 Da

-
Macromolecule #3: HEPTANE

MacromoleculeName: HEPTANE / type: ligand / ID: 3 / Number of copies: 2 / Formula: HP6
Molecular weightTheoretical: 100.202 Da
Chemical component information

ChemComp-HP6:
HEPTANE

-
Macromolecule #4: TETRADECANE

MacromoleculeName: TETRADECANE / type: ligand / ID: 4 / Number of copies: 2 / Formula: C14
Molecular weightTheoretical: 198.388 Da
Chemical component information

ChemComp-C14:
TETRADECANE

-
Experimental details

-
Structure determination

Methodcryo EM
Processingsingle particle reconstruction
Aggregation stateparticle

-
Sample preparation

BufferpH: 7.2
VitrificationCryogen name: ETHANE

-
Electron microscopy

MicroscopeFEI TITAN KRIOS
Image recordingFilm or detector model: GATAN K3 BIOQUANTUM (6k x 4k) / Average electron dose: 50.0 e/Å2
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 2.0 µm / Nominal defocus min: 1.2 µm
Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company

-
Image processing

Startup modelType of model: OTHER
Final reconstructionResolution.type: BY AUTHOR / Resolution: 3.07 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 220000
Initial angle assignmentType: ANGULAR RECONSTITUTION
Final angle assignmentType: ANGULAR RECONSTITUTION

+
About Yorodumi

-
News

-
Feb 9, 2022. New format data for meta-information of EMDB entries

New format data for meta-information of EMDB entries

  • Version 3 of the EMDB header file is now the official format.
  • The previous official version 1.9 will be removed from the archive.

Related info.:EMDB header

External links:wwPDB to switch to version 3 of the EMDB data model

-
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

-
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