[English] 日本語
Yorodumi
- EMDB-18842: Cryo-EM structure of 1-deoxy-D-xylulose 5-phosphate synthase (DXP... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: EMDB / ID: EMD-18842
TitleCryo-EM structure of 1-deoxy-D-xylulose 5-phosphate synthase (DXPS) from Plasmodium falciparum
Map data
Sample
  • Complex: Dimer of 1-deoxy-D-xylulose 5-phosphate synthase with Thiamin diphosphate bound.
    • Protein or peptide: 1-deoxy-D-xylulose-5-phosphate synthase
  • Ligand: MAGNESIUM ION
  • Ligand: THIAMINE DIPHOSPHATE
Keywords1-deoxy-D-xylulose 5-phosphate synthase / thiamin di-phosphate complex / transketolase / TRANSFERASE
Function / homology
Function and homology information


1-deoxy-D-xylulose-5-phosphate synthase / 1-deoxy-D-xylulose 5-phosphate biosynthetic process / 1-deoxy-D-xylulose-5-phosphate synthase activity / thiamine biosynthetic process / terpenoid biosynthetic process / membrane / metal ion binding
Similarity search - Function
Deoxyxylulose-5-phosphate synthase / 1-deoxy-D-xylulose-5-phosphate synthase / Transketolase, C-terminal domain / Transketolase binding site / Transketolase signature 2. / Transketolase, C-terminal domain / Transketolase-like, pyrimidine-binding domain / Transketolase, pyrimidine binding domain / Transketolase, pyrimidine binding domain / Transketolase C-terminal/Pyruvate-ferredoxin oxidoreductase domain II / Thiamin diphosphate-binding fold
Similarity search - Domain/homology
1-deoxy-D-xylulose-5-phosphate synthase
Similarity search - Component
Biological speciesPlasmodium falciparum (malaria parasite P. falciparum)
Methodsingle particle reconstruction / cryo EM / Resolution: 2.42 Å
AuthorsGawriljuk VO / Godoy AS / Oerlemans R / Groves MR
Funding supportEuropean Union, United Kingdom, 2 items
OrganizationGrant numberCountry
H2020 Marie Curie Actions of the European Commission860816European Union
Medical Research Council (MRC, United Kingdom)218785/Z/19/Z United Kingdom
CitationJournal: Nat Commun / Year: 2024
Title: Cryo-EM structure of 1-deoxy-D-xylulose 5-phosphate synthase DXPS from Plasmodium falciparum reveals a distinct N-terminal domain.
Authors: Victor O Gawriljuk / Andre S Godoy / Rick Oerlemans / Luise A T Welker / Anna K H Hirsch / Matthew R Groves /
Abstract: Plasmodium falciparum is the main causative agent of malaria, a deadly disease that mainly affects children under five years old. Artemisinin-based combination therapies have been pivotal in ...Plasmodium falciparum is the main causative agent of malaria, a deadly disease that mainly affects children under five years old. Artemisinin-based combination therapies have been pivotal in controlling the disease, but resistance has arisen in various regions, increasing the risk of treatment failure. The non-mevalonate pathway is essential for the isoprenoid synthesis in Plasmodium and provides several under-explored targets to be used in the discovery of new antimalarials. 1-deoxy-D-xylulose-5-phosphate synthase (DXPS) is the first and rate-limiting enzyme of the pathway. Despite its importance, there are no structures available for any Plasmodium spp., due to the complex sequence which contains large regions of high disorder, making crystallisation a difficult task. In this manuscript, we use cryo-electron microscopy to solve the P. falciparum DXPS structure at a final resolution of 2.42 Å. Overall, the structure resembles other DXPS enzymes but includes a distinct N-terminal domain exclusive to the Plasmodium genus. Mutational studies show that destabilization of the cap domain interface negatively impacts protein stability and activity. Additionally, a density for the co-factor thiamine diphosphate is found in the active site. Our work highlights the potential of cryo-EM to obtain structures of P. falciparum proteins that are unfeasible by means of crystallography.
History
DepositionNov 6, 2023-
Header (metadata) releaseJun 12, 2024-
Map releaseJun 12, 2024-
UpdateAug 14, 2024-
Current statusAug 14, 2024Processing site: PDBe / Status: Released

-
Structure visualization

Supplemental images

emd_18842.png

Downloads & links

-
Map

FileDownload / File: emd_18842.map.gz / Format: CCP4 / Size: 244.1 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Projections & slices

Image control

Size
Brightness
Contrast
Others
AxesZ (Sec.)Y (Row.)X (Col.)
0.74 Å/pix.
x 400 pix.
= 296. Å		0.74 Å/pix.
x 400 pix.
= 296. Å		0.74 Å/pix.
x 400 pix.
= 296. Å

Surface

Projections

Slices (1/3)

Slices (1/2)

Slices (2/3)

Images are generated by Spider.

Voxel sizeX=Y=Z: 0.74 Å
Density

Histogram

Histogram (log scale)
Contour LevelBy AUTHOR: 0.2
Minimum - Maximum-0.059852377 - 2.205356
Average (Standard dev.)0.0009618149 (±0.021254776)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions400400400
Spacing400400400
CellA=B=C: 296.0 Å
α=β=γ: 90.0 °

-
Supplemental data

-
Mask #1

Fileemd_18842_msk_1.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

-
Additional map: #1

Fileemd_18842_additional_1.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

-
Half map: #2

Fileemd_18842_half_map_1.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

-
Half map: #1

Fileemd_18842_half_map_2.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

-
Sample components

-
Entire : Dimer of 1-deoxy-D-xylulose 5-phosphate synthase with Thiamin dip...

EntireName: Dimer of 1-deoxy-D-xylulose 5-phosphate synthase with Thiamin diphosphate bound.
Components
  • Complex: Dimer of 1-deoxy-D-xylulose 5-phosphate synthase with Thiamin diphosphate bound.
    • Protein or peptide: 1-deoxy-D-xylulose-5-phosphate synthase
  • Ligand: MAGNESIUM ION
  • Ligand: THIAMINE DIPHOSPHATE

-
Supramolecule #1: Dimer of 1-deoxy-D-xylulose 5-phosphate synthase with Thiamin dip...

SupramoleculeName: Dimer of 1-deoxy-D-xylulose 5-phosphate synthase with Thiamin diphosphate bound.
type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1
Source (natural)Organism: Plasmodium falciparum (malaria parasite P. falciparum)

-
Macromolecule #1: 1-deoxy-D-xylulose-5-phosphate synthase

MacromoleculeName: 1-deoxy-D-xylulose-5-phosphate synthase / type: protein_or_peptide / ID: 1 / Number of copies: 2 / Enantiomer: LEVO
Source (natural)Organism: Plasmodium falciparum (malaria parasite P. falciparum)
Molecular weightTheoretical: 105.953609 KDa
Recombinant expressionOrganism: Escherichia coli BL21(DE3) (bacteria)
SequenceString: MGSSHHHHHH SSGLVPRGSH MYDIGKYFKQ INTFINIDEY KTIYGDEIYK EIYELYVERN IPEYYERKYF SEDIKKSVLF DIDKYNDVE FEKAIKEEFI NNGVYINNID NTYYKKENIL IMKKILHYFP LLKLINNPSD LKKLKKQYLP LLAHELKIFL F FIVNITGG ...String:
MGSSHHHHHH SSGLVPRGSH MYDIGKYFKQ INTFINIDEY KTIYGDEIYK EIYELYVERN IPEYYERKYF SEDIKKSVLF DIDKYNDVE FEKAIKEEFI NNGVYINNID NTYYKKENIL IMKKILHYFP LLKLINNPSD LKKLKKQYLP LLAHELKIFL F FIVNITGG HFSSVLSSLE IQLLLLYIFN QPYDNVIYDI GHQAYVHKIL TGRKLLFLSL RNKKGISGFL NIFESIYDKF GA GHSSTSL SAIQGYYEAE WQVKNKEKYG NGDIEISDNA NVTNNERIFQ KGIHNDNNIN NNINNNNYIN PSDVVGRENT NVP NVRNDN HNVDKVHIAI IGDGGLTGGM ALEALNYISF LNSKILIIYN DNGQVSLPTN AVSISGNRPI GSISDHLHYF VSNI EANAG DNKLSKNAKE NNIFENLNYD YIGVVNGNNT EELFKVLNNI KENKLKRATV LHVRTKKSND FINSKSPISI LHSIK KNEI FPFDTTILNG NIHKENKIEE EKNVSSSTKY DVNNKNNKNN DNSEIIKYED MFSKETFTDI YTNEMLKYLK KDRNII FLS PAMLGGSGLV KISERYPNNV YDVGIAEQHS VTFAAAMAMN KKLKIQLCIY STFLQRAYDQ IIHDLNLQNI PLKVIIG RS GLVGEDGATH QGIYDLSYLG TLNNAYIISP SNQVDLKRAL RFAYLDKDHS VYIRIPRMNI LSDKYMKGYL NIHMKNES K NIDVNVDIND DVDKYSEEYM DDDNFIKSFI GKSRIIKMDN ENNNTNEHYS SRGDTQTKKK KVCIFNMGSM LFNVINAIK EIEKEQYISH NYSFSIVDMI FLNPLDKNMI DHVIKQNKHQ YLITYEDNTI GGFSTHFNNY LIENNYITKH NLYVHNIYLS NEPIEHASF KDQQEVVKMD KCSLVNRIKN YLKNNPT

UniProtKB: 1-deoxy-D-xylulose-5-phosphate synthase

-
Macromolecule #2: MAGNESIUM ION

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

-
Macromolecule #3: THIAMINE DIPHOSPHATE

MacromoleculeName: THIAMINE DIPHOSPHATE / type: ligand / ID: 3 / Number of copies: 2 / Formula: TPP
Molecular weightTheoretical: 425.314 Da
Chemical component information

ChemComp-TPP:
THIAMINE DIPHOSPHATE

-
Experimental details

-
Structure determination

Methodcryo EM
Processingsingle particle reconstruction
Aggregation stateparticle

-
Sample preparation

Concentration0.9 mg/mL
BufferpH: 7.5
VitrificationCryogen name: ETHANE

-
Electron microscopy

MicroscopeFEI TITAN KRIOS
Image recordingFilm or detector model: TFS FALCON 4i (4k x 4k) / Average electron dose: 44.47 e/Å2
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 2.4 µm / Nominal defocus min: 0.8 µm
Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company

+
Image processing

Startup modelType of model: NONE
Final reconstructionNumber classes used: 2 / Applied symmetry - Point group: C2 (2 fold cyclic) / Algorithm: FOURIER SPACE / Resolution.type: BY AUTHOR / Resolution: 2.42 Å / Resolution method: FSC 0.143 CUT-OFF
Software: (Name: Coot (ver. 0.9.6), PHENIX (ver. 1.20.1-4487))
Number images used: 97205
Initial angle assignmentType: MAXIMUM LIKELIHOOD / Software - Name: cryoSPARC (ver. 4.1.2)
Final angle assignmentType: MAXIMUM LIKELIHOOD / Software - Name: cryoSPARC (ver. 4.1.2)
FSC plot (resolution estimation)

-
Atomic model buiding 1

Initial modelPDB ID:

6694


Chain - Source name: AlphaFold / Chain - Initial model type: in silico model
Output model

PDB-8r2h:
Cryo-EM structure of 1-deoxy-D-xylulose 5-phosphate synthase (DXPS) from Plasmodium falciparum

+
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