[English] 日本語
Yorodumi
- EMDB-62765: cryo-EM structure of Vitamin K-dependent gamma-carboxylase comple... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: EMDB / ID: EMD-62765
Titlecryo-EM structure of Vitamin K-dependent gamma-carboxylase complexed with factor IX
Map data
Sample
  • Complex: Vitamin K-dependent gamma-carboxylase complexed with factor IX
    • Protein or peptide: Vitamin K-dependent gamma-carboxylase
    • Protein or peptide: Coagulation factor IX
  • Ligand: 2-acetamido-2-deoxy-beta-D-glucopyranose
  • Ligand: vitamin K1 hydroquinone
  • Ligand: BICARBONATE ION
  • Ligand: CARBON DIOXIDE
  • Ligand: CHOLESTEROL
  • Ligand: 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine
  • Ligand: CHOLESTEROL HEMISUCCINATE
  • Ligand: water
KeywordsMEMBRANE PROTEIN
Function / homology
Function and homology information


peptidyl-glutamate 4-carboxylase / gamma-glutamyl carboxylase activity / negative regulation of testosterone biosynthetic process / Defective F9 secretion / coagulation factor IXa / negative regulation of bone development / Defective gamma-carboxylation of F9 / vitamin binding / vitamin K metabolic process / Defective F9 activation ...peptidyl-glutamate 4-carboxylase / gamma-glutamyl carboxylase activity / negative regulation of testosterone biosynthetic process / Defective F9 secretion / coagulation factor IXa / negative regulation of bone development / Defective gamma-carboxylation of F9 / vitamin binding / vitamin K metabolic process / Defective F9 activation / negative regulation of neurotransmitter secretion / Defective factor IX causes thrombophilia / Defective cofactor function of FVIIIa variant / Defective F9 variant does not activate FX / type B pancreatic cell proliferation / : / zymogen activation / Protein hydroxylation / Transport of gamma-carboxylated protein precursors from the endoplasmic reticulum to the Golgi apparatus / Gamma-carboxylation of protein precursors / Removal of aminoterminal propeptides from gamma-carboxylated proteins / : / protein modification process / protein maturation / Golgi lumen / cellular response to insulin stimulus / blood coagulation / glucose homeostasis / extracellular matrix / endopeptidase activity / endoplasmic reticulum lumen / serine-type endopeptidase activity / calcium ion binding / endoplasmic reticulum membrane / proteolysis / : / extracellular exosome / extracellular region / membrane / metal ion binding / plasma membrane
Similarity search - Function
Vitamin K-dependent gamma-carboxylase / HTTM / : / : / HTTM domain / Vitamin K-dependent gamma-carboxylase, lumenal domain / Horizontally Transferred TransMembrane Domain / Peptidase S1A, coagulation factor VII/IX/X/C/Z / : / Coagulation factor-like, Gla domain superfamily ...Vitamin K-dependent gamma-carboxylase / HTTM / : / : / HTTM domain / Vitamin K-dependent gamma-carboxylase, lumenal domain / Horizontally Transferred TransMembrane Domain / Peptidase S1A, coagulation factor VII/IX/X/C/Z / : / Coagulation factor-like, Gla domain superfamily / Coagulation Factor Xa inhibitory site / EGF-like domain / RmlC-like cupin domain superfamily / EGF-type aspartate/asparagine hydroxylation site / EGF-like calcium-binding, conserved site / Calcium-binding EGF-like domain signature. / Aspartic acid and asparagine hydroxylation site. / EGF-like calcium-binding domain / Calcium-binding EGF-like domain / Vitamin K-dependent carboxylation/gamma-carboxyglutamic (GLA) domain / Gamma-carboxyglutamic acid-rich (GLA) domain / Gamma-carboxyglutamic acid-rich (GLA) domain superfamily / Vitamin K-dependent carboxylation domain. / Gla domain profile. / Domain containing Gla (gamma-carboxyglutamate) residues. / Epidermal growth factor-like domain. / EGF-like domain profile. / EGF-like domain signature 1. / EGF-like domain signature 2. / EGF-like domain / RmlC-like jelly roll fold / Serine proteases, trypsin family, histidine active site / Serine proteases, trypsin family, serine active site / Serine proteases, trypsin family, histidine active site. / Peptidase S1A, chymotrypsin family / Serine proteases, trypsin family, serine active site. / Serine proteases, trypsin domain profile. / Trypsin-like serine protease / Serine proteases, trypsin domain / Trypsin / Peptidase S1, PA clan, chymotrypsin-like fold / Peptidase S1, PA clan
Similarity search - Domain/homology
Coagulation factor IX / Vitamin K-dependent gamma-carboxylase
Similarity search - Component
Biological speciesHomo sapiens (human)
Methodsingle particle reconstruction / cryo EM / Resolution: 2.62 Å
AuthorsYao D / Wu K / Lan P
Funding support China, 1 items
OrganizationGrant numberCountry
National Natural Science Foundation of China (NSFC) China
CitationJournal: Nat Commun / Year: 2025
Title: Structural insight into bicarbonate-mediated carboxylation by human vitamin K-dependent carboxylase.
Authors: Ke Wu / Zheng Wang / Deqiang Yao / Shaobai Li / Xiaozhu Wang / Yuanyuan Zhang / Mi Cao / Yafeng Shen / Shunpeng Xing / Jian Wu / Ming Lei / Pengfei Lan /
Abstract: Vitamin K-dependent (VKD) carboxylation, mediated by γ-glutamyl carboxylase (GGCX), is essential for the maturation of VKD proteins involved in critical physiological processes such as blood ...Vitamin K-dependent (VKD) carboxylation, mediated by γ-glutamyl carboxylase (GGCX), is essential for the maturation of VKD proteins involved in critical physiological processes such as blood clotting, vascular calcification and bone metabolism. Here, we present cryo-electron microscopic structures of human GGCX alone and in complex with VKD proteins, vitamin K, and inhibitor anisindione. GGCX specifically recognizes diverse VKD substrates through high-affinity propeptide binding, while substrates like osteocalcin utilize a secondary exosite to enhance interaction. GGCX employs a conserved dipeptide anchoring mechanism that ensures processive carboxylation of glutamate residues. GGCX undergoes allosteric conformational changes that enable coordinated binding of vitamin K and glutamate substrates, facilitating the catalytic process. Additionally, we reveal a bicarbonate-mediated CO₂ capture mechanism that is conserved across bacterial and eukaryotic species, suggesting that this strategy for CO₂ utilization is both ancient and universal. Our findings lay the foundation for developing targeted anticoagulant drugs and innovative enzymatic CO₂ fixation strategies.
History
DepositionDec 16, 2024-
Header (metadata) releaseOct 22, 2025-
Map releaseOct 22, 2025-
UpdateMay 6, 2026-
Current statusMay 6, 2026Processing site: PDBc / Status: Released

-
Structure visualization

Supplemental images

emd_62765.png

Downloads & links

-
Map

FileDownload / File: emd_62765.map.gz / Format: CCP4 / Size: 64 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Projections & slices

Image control

Size
Brightness
Contrast
Others
AxesZ (Sec.)Y (Row.)X (Col.)
1.1 Å/pix.
x 256 pix.
= 281.6 Å		1.1 Å/pix.
x 256 pix.
= 281.6 Å		1.1 Å/pix.
x 256 pix.
= 281.6 Å

Surface

Projections

Slices (1/3)

Slices (1/2)

Slices (2/3)

Images are generated by Spider.

Voxel sizeX=Y=Z: 1.1 Å
Density

Histogram

Histogram (log scale)
Contour LevelBy AUTHOR: 0.3
Minimum - Maximum-5.223652 - 6.935541
Average (Standard dev.)-0.00093734387 (±0.08584506)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions256256256
Spacing256256256
CellA=B=C: 281.6 Å
α=β=γ: 90.0 °

-
Supplemental data

-
Half map: #2

Fileemd_62765_half_map_1.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

-
Half map: #1

Fileemd_62765_half_map_2.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

-
Sample components

+
Entire : Vitamin K-dependent gamma-carboxylase complexed with factor IX

EntireName: Vitamin K-dependent gamma-carboxylase complexed with factor IX
Components
  • Complex: Vitamin K-dependent gamma-carboxylase complexed with factor IX
    • Protein or peptide: Vitamin K-dependent gamma-carboxylase
    • Protein or peptide: Coagulation factor IX
  • Ligand: 2-acetamido-2-deoxy-beta-D-glucopyranose
  • Ligand: vitamin K1 hydroquinone
  • Ligand: BICARBONATE ION
  • Ligand: CARBON DIOXIDE
  • Ligand: CHOLESTEROL
  • Ligand: 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine
  • Ligand: CHOLESTEROL HEMISUCCINATE
  • Ligand: water

+
Supramolecule #1: Vitamin K-dependent gamma-carboxylase complexed with factor IX

SupramoleculeName: Vitamin K-dependent gamma-carboxylase complexed with factor IX
type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#2
Source (natural)Organism: Homo sapiens (human)

+
Macromolecule #1: Vitamin K-dependent gamma-carboxylase

MacromoleculeName: Vitamin K-dependent gamma-carboxylase / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO / EC number: peptidyl-glutamate 4-carboxylase
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 81.404992 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: SRIGKLLGFE WTDLSSWRRL VTLLNRPTDP ASLAVFRFLF GFLMVLDIPQ ERGLSSLDRK YLDGLDVCRF PLLDALRPLP LDWMYLVYT IMFLGALGMM LGLCYRISCV LFLLPYWYVF LLDKTSWNNH SYLYGLLAFQ LTFMDANHYW SVDGLLNAHR R NAHVPLWN ...String:
SRIGKLLGFE WTDLSSWRRL VTLLNRPTDP ASLAVFRFLF GFLMVLDIPQ ERGLSSLDRK YLDGLDVCRF PLLDALRPLP LDWMYLVYT IMFLGALGMM LGLCYRISCV LFLLPYWYVF LLDKTSWNNH SYLYGLLAFQ LTFMDANHYW SVDGLLNAHR R NAHVPLWN YAVLRGQIFI VYFIAGVKKL DADWVEGYSM EYLSRHWLFS PFKLLLSEEL TSLLVVHWGG LLLDLSAGFL LF FDVSRSI GLFFVSYFHC MNSQLFSIGM FSYVMLASSP LFCSPEWPRK LVSYCPRRLQ QLLPLKAAPQ PSVSCVYKRS RGK SGQKPG LRHQLGAAFT LLYLLEQLFL PYSHFLTQGY NNWTNGLYGY SWDMMVHSRS HQHVKITYRD GRTGELGYLN PGVF TQSRR WKDHADMLKQ YATCLSRLLP KYNVTEPQIY FDIWVSINDR FQQRIFDPRV DIVQAAWSPF QRTSWVQPLL MDLSP WRAK LQEIKSSLDN HTEVVFIADF PGLHLENFVS EDLGNTSIQL LQGEVTVELV AEQKNQTLRE GEKMQLPAGE YHKVYT TSP SPSCYMYVYV NTTELALEQD LAYLQELKEK VENGSETGPL PPELQPLLEG EVKGGPEPTP LVQTFLRRQQ RLQEIER RR NTPFHERFFR FLLRKLYVFR RSFLMTCISL RNLILGRPSL EQLAQEVTYA NLRPFE

UniProtKB: Vitamin K-dependent gamma-carboxylase

+
Macromolecule #2: Coagulation factor IX

MacromoleculeName: Coagulation factor IX / type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO / EC number: coagulation factor IXa
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 3.338769 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString:
TVFLDHENAN KILNRPKRYN SGKLEEFV

UniProtKB: Coagulation factor IX

+
Macromolecule #4: 2-acetamido-2-deoxy-beta-D-glucopyranose

MacromoleculeName: 2-acetamido-2-deoxy-beta-D-glucopyranose / type: ligand / ID: 4 / Number of copies: 1 / Formula: NAG
Molecular weightTheoretical: 221.208 Da
Chemical component information

ChemComp-NAG:
2-acetamido-2-deoxy-beta-D-glucopyranose

+
Macromolecule #5: vitamin K1 hydroquinone

MacromoleculeName: vitamin K1 hydroquinone / type: ligand / ID: 5 / Number of copies: 1 / Formula: A1AVC
Molecular weightTheoretical: 452.712 Da

+
Macromolecule #6: BICARBONATE ION

MacromoleculeName: BICARBONATE ION / type: ligand / ID: 6 / Number of copies: 1 / Formula: BCT
Molecular weightTheoretical: 61.017 Da
Chemical component information

ChemComp-BCT:
BICARBONATE ION

+
Macromolecule #7: CARBON DIOXIDE

MacromoleculeName: CARBON DIOXIDE / type: ligand / ID: 7 / Number of copies: 1 / Formula: CO2
Molecular weightTheoretical: 44.01 Da
Chemical component information

ChemComp-CO2:
CARBON DIOXIDE

+
Macromolecule #8: CHOLESTEROL

MacromoleculeName: CHOLESTEROL / type: ligand / ID: 8 / Number of copies: 1 / Formula: CLR
Molecular weightTheoretical: 386.654 Da
Chemical component information

ChemComp-CLR:
CHOLESTEROL

+
Macromolecule #9: 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine

MacromoleculeName: 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine / type: ligand / ID: 9 / Number of copies: 3 / Formula: PEE
Molecular weightTheoretical: 744.034 Da
Chemical component information

ChemComp-PEE:
1,2-dioleoyl-sn-glycero-3-phosphoethanolamine / DOPE, phospholipid*YM

+
Macromolecule #10: CHOLESTEROL HEMISUCCINATE

MacromoleculeName: CHOLESTEROL HEMISUCCINATE / type: ligand / ID: 10 / Number of copies: 1 / Formula: Y01
Molecular weightTheoretical: 486.726 Da
Chemical component information

ChemComp-Y01:
CHOLESTEROL HEMISUCCINATE

+
Macromolecule #11: water

MacromoleculeName: water / type: ligand / ID: 11 / Number of copies: 24 / Formula: HOH
Molecular weightTheoretical: 18.015 Da
Chemical component information

ChemComp-HOH:
WATER

-
Experimental details

-
Structure determination

Methodcryo EM
Processingsingle particle reconstruction
Aggregation stateparticle

-
Sample preparation

BufferpH: 7.5
VitrificationCryogen name: ETHANE

-
Electron microscopy

MicroscopeFEI/PHILIPS CM300FEG/T
Image recordingFilm or detector model: GATAN K3 (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: 1.7 µm / Nominal defocus min: 0.9 µm

+
Image processing

CTF correctionType: PHASE FLIPPING AND AMPLITUDE CORRECTION
Startup modelType of model: NONE
Final reconstructionResolution.type: BY AUTHOR / Resolution: 2.62 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 680930
Initial angle assignmentType: RANDOM ASSIGNMENT
Final angle assignmentType: MAXIMUM LIKELIHOOD
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