[English] 日本語
Yorodumi
- EMDB-71076: Human liver phosphofructokinase-1 bound to XJ-4-85 -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: EMDB / ID: EMD-71076
TitleHuman liver phosphofructokinase-1 bound to XJ-4-85
Map dataPFKL monomer bound to XJ-4-85, density modified
Sample
  • Complex: PFKL monomer
    • Protein or peptide: ATP-dependent 6-phosphofructokinase, liver type
  • Ligand: 5-[bis(oxidanylidene)-$l^{5}-sulfanyl]-1,3-benzodioxole
  • Ligand: 1,6-di-O-phosphono-beta-D-fructofuranose
  • Ligand: ADENOSINE-5'-DIPHOSPHATE
  • Ligand: 6-O-phosphono-beta-D-fructofuranose
  • Ligand: 4-[bis(3,4-difluorophenyl)methylidene]piperidine
Keywordsphosphofructokinase-1 / liver / PFKL / activator / TRANSFERASE
Function / homology
Function and homology information


6-phosphofructokinase complex / 6-phosphofructokinase / fructose binding / 6-phosphofructokinase activity / fructose-6-phosphate binding / fructose 1,6-bisphosphate metabolic process / fructose 6-phosphate metabolic process / Glycolysis / canonical glycolysis / response to glucose ...6-phosphofructokinase complex / 6-phosphofructokinase / fructose binding / 6-phosphofructokinase activity / fructose-6-phosphate binding / fructose 1,6-bisphosphate metabolic process / fructose 6-phosphate metabolic process / Glycolysis / canonical glycolysis / response to glucose / glycolytic process / kinase binding / secretory granule lumen / ficolin-1-rich granule lumen / Neutrophil degranulation / extracellular exosome / extracellular region / ATP binding / membrane / identical protein binding / cytosol
Similarity search - Function
ATP-dependent 6-phosphofructokinase, vertebrate-type / ATP-dependent 6-phosphofructokinase, eukaryotic-type / Phosphofructokinase, conserved site / Phosphofructokinase signature. / Phosphofructokinase domain / ATP-dependent 6-phosphofructokinase / Phosphofructokinase superfamily / Phosphofructokinase
Similarity search - Domain/homology
ATP-dependent 6-phosphofructokinase, liver type
Similarity search - Component
Biological speciesHomo sapiens (human)
Methodsingle particle reconstruction / cryo EM / Resolution: 3.2 Å
AuthorsLynch EM / Jiang X / Hsu K-L / Kollman JM
Funding support United States, 2 items
OrganizationGrant numberCountry
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)R35GM149542 United States
National Institutes of Health/Office of the DirectorS10OD023476 United States
CitationJournal: Nat Chem Biol / Year: 2026
Title: A covalent PFKL activator suppresses tumor growth.
Authors: Xiaoding Jiang / Eric M Lynch / Congcong Lyu / Crystal N Wilson / Lauren E Salay / Hayden T Hess / Scott N Lyons / Mu-Jie Lu / Shuangyu Luo / Gibae Kim / Hsin-Ru Chan / Wesley J Wolfe / ...Authors: Xiaoding Jiang / Eric M Lynch / Congcong Lyu / Crystal N Wilson / Lauren E Salay / Hayden T Hess / Scott N Lyons / Mu-Jie Lu / Shuangyu Luo / Gibae Kim / Hsin-Ru Chan / Wesley J Wolfe / Lauren G Zacharias / Thomas P Mathews / Yi-Chih Lin / Bradley A Webb / Justin M Kollman / Xiaolu A Cambronne / Ku-Lung Hsu /
Abstract: Glycolysis fuels vital cellular functions, and its dysregulation has been implicated in cancer, neurodegeneration, antibiotic resistance and diabetes. The glycolytic dependency of cancer, known as ...Glycolysis fuels vital cellular functions, and its dysregulation has been implicated in cancer, neurodegeneration, antibiotic resistance and diabetes. The glycolytic dependency of cancer, known as the Warburg effect, represents a key vulnerability for development of targeted anticancer agents; however, the development of such agents remains challenging owing to metabolic heterogeneity and resistance. Here we developed a covalent phosphofructokinase-1 liver type (PFKL) activator that couples glycolytic activation with delivery of a cytotoxic carnitine palmitoyltransferase 2 (CPT2)-targeting payload to cancer cells in vitro and in vivo. The electrophile-drug conjugate site-specifically and proteome-wide selectively modifies K677 in the allosteric effector site to stabilize the R-state tetramer of PFKL, while concomitantly releasing a CPT2-selective inhibitor to destabilize cell metabolism. The delivery mechanism of electrophile-drug conjugates is analogous to that of antibody-drug conjugates, but differentiated by their selective covalent targeting of intracellular proteins.
History
DepositionJun 6, 2025-
Header (metadata) releaseSep 23, 2026-
Map releaseSep 23, 2026-
UpdateSep 23, 2026-
Current statusSep 23, 2026Processing site: RCSB / Status: Released

-
Structure visualization

Supplemental images

emd_71076.png

Downloads & links

-
Map

FileDownload / File: emd_71076.map.gz / Format: CCP4 / Size: 244.1 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
AnnotationPFKL monomer bound to XJ-4-85, density modified
Projections & slices

Image control

Size
Brightness
Contrast
Others
AxesX (Sec.)Y (Row.)Z (Col.)
0.89 Å/pix.
x 400 pix.
= 354. Å		0.89 Å/pix.
x 400 pix.
= 354. Å		0.89 Å/pix.
x 400 pix.
= 354. Å

Surface

Projections

Slices (1/3)

Slices (1/2)

Slices (2/3)

Images are generated by Spider.

Voxel sizeX=Y=Z: 0.885 Å
Density

Histogram

Histogram (log scale)
Contour LevelBy AUTHOR: 1.6
Minimum - Maximum-9.174875999999999 - 13.848513000000001
Average (Standard dev.)-0.000003877389 (±0.189973)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderZYX
Origin000
Dimensions400400400
Spacing400400400
CellA=B=C: 354.0 Å
α=β=γ: 90.0 °

-
Supplemental data

-
Additional map: PFKL monomer bound to XJ-4-85, b-factor sharpened

Fileemd_71076_additional_1.map
AnnotationPFKL monomer bound to XJ-4-85, b-factor sharpened
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

-
Half map: #2

Fileemd_71076_half_map_1.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

-
Half map: #1

Fileemd_71076_half_map_2.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

-
Sample components

-
Entire : PFKL monomer

EntireName: PFKL monomer
Components
  • Complex: PFKL monomer
    • Protein or peptide: ATP-dependent 6-phosphofructokinase, liver type
  • Ligand: 5-[bis(oxidanylidene)-$l^{5}-sulfanyl]-1,3-benzodioxole
  • Ligand: 1,6-di-O-phosphono-beta-D-fructofuranose
  • Ligand: ADENOSINE-5'-DIPHOSPHATE
  • Ligand: 6-O-phosphono-beta-D-fructofuranose
  • Ligand: 4-[bis(3,4-difluorophenyl)methylidene]piperidine

-
Supramolecule #1: PFKL monomer

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

-
Macromolecule #1: ATP-dependent 6-phosphofructokinase, liver type

MacromoleculeName: ATP-dependent 6-phosphofructokinase, liver type / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO / EC number: 6-phosphofructokinase
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 80.72725 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: GAGKAIGVLT SGGDAQGMNA AVRAVTRMGI YVGAKVFLIY EGYEGLVEGG ENIKQANWLS VSNIIQLGGT IIGSARCKAF TTREGRRAA AYNLVQHGIT NLCVIGGDGS LTGANIFRSE WGSLLEELVA EGKISETTAR TYSHLNIAGL VGSIDNDFCG T DMTIGTDS ...String:
GAGKAIGVLT SGGDAQGMNA AVRAVTRMGI YVGAKVFLIY EGYEGLVEGG ENIKQANWLS VSNIIQLGGT IIGSARCKAF TTREGRRAA AYNLVQHGIT NLCVIGGDGS LTGANIFRSE WGSLLEELVA EGKISETTAR TYSHLNIAGL VGSIDNDFCG T DMTIGTDS ALHRIMEVID AITTTAQSHQ RTFVLEVMGR HCGYLALVSA LASGADWLFI PEAPPEDGWE NFMCERLGET RS RGSRLNI IIIAEGAIDR NGKPISSSYV KDLVVQRLGF DTRVTVLGHV QRGGTPSAFD RILSSKMGME AVMALLEATP DTP ACVVTL SGNQSVRLPL MECVQMTKEV QKAMDDKRFD EATQLRGGSF ENNWNIYKLL AHQKPPKEKS NFSLAILNVG APAA GMNAA VRSAVRTGIS HGHTVYVVHD GFEGLAKGQV QEVGWHDVAG WLGRGGSMLG TKRTLPKGQL ESIVENIRIY GIHAL LVVG GFEAYEGVLQ LVEARGRYEE LCIVMCVIPA TISNNVPGTD FSLGSDTAVN AAMESCDRIK QSASGTKRRV FIVETM GGY CGYLATVTGI AVGADAAYVF EDPFNIHDLK VNVEHMTEKM KTDIQRGLVL RNEKCHDYYT TEFLYNLYSS EGKGVFD CR TNVLGHLQQG GAPTPFDRNY GTKLGVKAML WLSEKLREVY RKGRVFANAP DSACVIGLKK KAVAFSPVTE LKKDTDFE H RMPREQWWLS LRLMLKMLAQ

UniProtKB: ATP-dependent 6-phosphofructokinase, liver type

-
Macromolecule #2: 5-[bis(oxidanylidene)-$l^{5}-sulfanyl]-1,3-benzodioxole

MacromoleculeName: 5-[bis(oxidanylidene)-$l^{5}-sulfanyl]-1,3-benzodioxole
type: ligand / ID: 2 / Number of copies: 1 / Formula: A1C4X
Molecular weightTheoretical: 201.2 Da

-
Macromolecule #3: 1,6-di-O-phosphono-beta-D-fructofuranose

MacromoleculeName: 1,6-di-O-phosphono-beta-D-fructofuranose / type: ligand / ID: 3 / Number of copies: 1 / Formula: FBP
Molecular weightTheoretical: 340.116 Da
Chemical component information

ChemComp-FBP:
1,6-di-O-phosphono-beta-D-fructofuranose

-
Macromolecule #4: ADENOSINE-5'-DIPHOSPHATE

MacromoleculeName: ADENOSINE-5'-DIPHOSPHATE / type: ligand / ID: 4 / Number of copies: 1 / Formula: ADP
Molecular weightTheoretical: 427.201 Da
Chemical component information

ChemComp-ADP:
ADENOSINE-5'-DIPHOSPHATE / ADP, energy-carrying molecule*YM

-
Macromolecule #5: 6-O-phosphono-beta-D-fructofuranose

MacromoleculeName: 6-O-phosphono-beta-D-fructofuranose / type: ligand / ID: 5 / Number of copies: 1 / Formula: F6P
Molecular weightTheoretical: 260.136 Da
Chemical component information

ChemComp-F6P:
6-O-phosphono-beta-D-fructofuranose

-
Macromolecule #6: 4-[bis(3,4-difluorophenyl)methylidene]piperidine

MacromoleculeName: 4-[bis(3,4-difluorophenyl)methylidene]piperidine / type: ligand / ID: 6 / Number of copies: 1 / Formula: A1CFQ
Molecular weightTheoretical: 321.312 Da

-
Experimental details

-
Structure determination

Methodcryo EM
Processingsingle particle reconstruction
Aggregation stateparticle

-
Sample preparation

BufferpH: 8
VitrificationCryogen name: ETHANE / Chamber humidity: 100 % / Instrument: FEI VITROBOT MARK IV

-
Electron microscopy

MicroscopeTFS GLACIOS
Image recordingFilm or detector model: GATAN K3 (6k x 4k) / Average electron dose: 42.0 e/Å2
Electron beamAcceleration voltage: 200 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 2.0 µm / Nominal defocus min: 0.8 µm
Sample stageCooling holder cryogen: NITROGEN

+
Image processing

CTF correctionSoftware - Name: cryoSPARC / Type: PHASE FLIPPING AND AMPLITUDE CORRECTION
Startup modelType of model: OTHER
Final reconstructionResolution.type: BY AUTHOR / Resolution: 3.2 Å / Resolution method: FSC 0.143 CUT-OFF / Software - Name: cryoSPARC / Number images used: 124715
Initial angle assignmentType: MAXIMUM LIKELIHOOD / Software - Name: cryoSPARC
Final angle assignmentType: MAXIMUM LIKELIHOOD / Software - Name: cryoSPARC
Final 3D classificationSoftware - Name: cryoSPARC
FSC plot (resolution estimation)

-
Atomic model buiding 1

RefinementSpace: REAL / Protocol: FLEXIBLE FIT
Output model

PDB-9p0j:
Human liver phosphofructokinase-1 bound to XJ-4-85

-
Atomic model buiding 2

RefinementSpace: REAL / Protocol: FLEXIBLE FIT
Output model

PDB-9p0j:
Human liver phosphofructokinase-1 bound to XJ-4-85

+
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