[English] 日本語
Yorodumi
- EMDB-11014: Cryo-EM map of human dihydrolipoamide succinyltransferase catalyt... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: EMDB / ID: EMD-11014
TitleCryo-EM map of human dihydrolipoamide succinyltransferase catalytic domain (DLST)
Map data
Sample
  • Complex: human dihydrolipoamide succinyltransferase (DLST)
    • Protein or peptide: human dihydrolipoamide succinyltransferase catalytic domain (DLST)
Biological speciesHomo sapiens (human)
Methodsingle particle reconstruction / cryo EM / Resolution: 4.7 Å
AuthorsBailey HJ / Bezerra GA / Foster W / McCorvie TJ / Saez LD / Yue WW
CitationJournal: IUCrJ / Year: 2020
Title: Crystal structure and interaction studies of human DHTKD1 provide insight into a mitochondrial megacomplex in lysine catabolism.
Authors: Gustavo A Bezerra / William R Foster / Henry J Bailey / Kevin G Hicks / Sven W Sauer / Bianca Dimitrov / Thomas J McCorvie / Jürgen G Okun / Jared Rutter / Stefan Kölker / Wyatt W Yue /
Abstract: DHTKD1 is a lesser-studied E1 enzyme among the family of 2-oxoacid de-hydrogenases. In complex with E2 (di-hydro-lipo-amide succinyltransferase, DLST) and E3 (dihydrolipo-amide de-hydrogenase, DLD) ...DHTKD1 is a lesser-studied E1 enzyme among the family of 2-oxoacid de-hydrogenases. In complex with E2 (di-hydro-lipo-amide succinyltransferase, DLST) and E3 (dihydrolipo-amide de-hydrogenase, DLD) components, DHTKD1 is involved in lysine and tryptophan catabolism by catalysing the oxidative de-carboxyl-ation of 2-oxoadipate (2OA) in mitochondria. Here, the 1.9 Å resolution crystal structure of human DHTKD1 is solved in complex with the thi-amine diphosphate co-factor. The structure reveals how the DHTKD1 active site is modelled upon the well characterized homologue 2-oxoglutarate (2OG) de-hydrogenase but engineered specifically to accommodate its preference for the longer substrate of 2OA over 2OG. A 4.7 Å resolution reconstruction of the human DLST catalytic core is also generated by single-particle electron microscopy, revealing a 24-mer cubic scaffold for assembling DHTKD1 and DLD protomers into a megacomplex. It is further demonstrated that missense DHTKD1 variants causing the inborn error of 2-amino-adipic and 2-oxoadipic aciduria impact on the complex formation, either directly by disrupting the interaction with DLST, or indirectly through destabilizing the DHTKD1 protein. This study provides the starting framework for developing DHTKD1 modulators to probe the intricate mitochondrial energy metabolism.
History
DepositionMay 7, 2020-
Header (metadata) releaseNov 18, 2020-
Map releaseNov 18, 2020-
UpdateNov 18, 2020-
Current statusNov 18, 2020Processing site: PDBe / Status: Released

-
Structure visualization

Movie
  • Surface view with section colored by density value
  • Surface level: 0.0233
  • Imaged by UCSF Chimera
  • Download
  • Surface view colored by radius
  • Surface level: 0.0233
  • Imaged by UCSF Chimera
  • Download
Movie viewer
Structure viewerEM map:
SurfViewMolmilJmol/JSmol
Supplemental images

emd_11014.png

Downloads & links

-
Map

FileDownload / File: emd_11014.map.gz / Format: CCP4 / Size: 155.3 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Voxel sizeX=Y=Z: 0.96 Å
Density
Contour LevelBy AUTHOR: 0.0233 / Movie #1: 0.0233
Minimum - Maximum-0.062817045 - 0.09612747
Average (Standard dev.)0.00048205853 (±0.0045434227)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions344344344
Spacing344344344
CellA=B=C: 330.24 Å
α=β=γ: 90.0 °

CCP4 map header:

modeImage stored as Reals
Å/pix. X/Y/Z0.960.960.96
M x/y/z344344344
origin x/y/z0.0000.0000.000
length x/y/z330.240330.240330.240
α/β/γ90.00090.00090.000
MAP C/R/S123
start NC/NR/NS000
NC/NR/NS344344344
D min/max/mean-0.0630.0960.000

-
Supplemental data

-
Sample components

-
Entire : human dihydrolipoamide succinyltransferase (DLST)

EntireName: human dihydrolipoamide succinyltransferase (DLST)
Components
  • Complex: human dihydrolipoamide succinyltransferase (DLST)
    • Protein or peptide: human dihydrolipoamide succinyltransferase catalytic domain (DLST)

-
Supramolecule #1: human dihydrolipoamide succinyltransferase (DLST)

SupramoleculeName: human dihydrolipoamide succinyltransferase (DLST) / type: complex / ID: 1 / Parent: 0 / Macromolecule list: all
Source (natural)Organism: Homo sapiens (human)
Recombinant expressionOrganism: Spodoptera frugiperda (fall armyworm)
Molecular weightTheoretical: 1.059 MDa

-
Macromolecule #1: human dihydrolipoamide succinyltransferase catalytic domain (DLST)

MacromoleculeName: human dihydrolipoamide succinyltransferase catalytic domain (DLST)
type: protein_or_peptide / ID: 1 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Recombinant expressionOrganism: Spodoptera frugiperda (fall armyworm)
SequenceString: MGHHHHHHSS GVDLGTENLY FQSMDDLVTV KTPAFAESVT EGDVRWEKAV GDTVAEDEVV CEIETDKTSV QVPSPANGVI EALLVPDGGK VEGGTPLFTL RKTGAAPAKA KPAEAPAAAA PKAEPTAAAV PPPAAPIPTQ MPPVPSPSQP PSGKPVSAVK PTVAPPLAEP ...String:
MGHHHHHHSS GVDLGTENLY FQSMDDLVTV KTPAFAESVT EGDVRWEKAV GDTVAEDEVV CEIETDKTSV QVPSPANGVI EALLVPDGGK VEGGTPLFTL RKTGAAPAKA KPAEAPAAAA PKAEPTAAAV PPPAAPIPTQ MPPVPSPSQP PSGKPVSAVK PTVAPPLAEP GAGKGLRSEH REKMNRMRQR IAQRLKEAQN TCAMLTTFNE IDMSNIQEMR ARHKEAFLKK HNLKLGFMSA FVKASAFALQ EQPVVNAVID DTTKEVVYRD YIDISVAVAT PRGLVVPVIR NVEAMNFADI ERTITELGEK ARKNELAIED MDGGTFTISN GGVFGSLFGT PIINPPQSAI LGMHGIFDRP VAIGGKVEVR PMMYVALTYD HRLIDGREAV TFLRKIKAAV EDPRVLLLDL

-
Experimental details

-
Structure determination

Methodcryo EM
Processingsingle particle reconstruction
Aggregation stateparticle

-
Sample preparation

Concentration0.2 mg/mL
BufferpH: 7.5
Component:
ConcentrationName
20.0 mMHepes
150.0 mMNaClSodium chloride
0.5 mMTCEP
VitrificationCryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 277.15 K

-
Electron microscopy

MicroscopeTFS GLACIOS
Electron beamAcceleration voltage: 200 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: OTHER / Imaging mode: OTHER / Nominal magnification: 150000
Image recordingFilm or detector model: FEI FALCON III (4k x 4k) / Detector mode: OTHER / Number grids imaged: 1 / Number real images: 619 / Average exposure time: 1.0 sec. / Average electron dose: 32.52 e/Å2

-
Image processing

Particle selectionNumber selected: 165739
CTF correctionSoftware - Name: CTFFIND
Initial angle assignmentType: MAXIMUM LIKELIHOOD / Software - Name: RELION (ver. 3.0)
Final 3D classificationNumber classes: 1 / Avg.num./class: 33072 / Software - Name: RELION (ver. 3.0)
Final angle assignmentType: MAXIMUM LIKELIHOOD
Final reconstructionApplied symmetry - Point group: O (octahedral) / Resolution.type: BY AUTHOR / Resolution: 4.7 Å / Resolution method: FSC 0.143 CUT-OFF / Software - Name: RELION (ver. 3.0) / Number images used: 3356
FSC plot (resolution estimation)

+
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