[English] 日本語
Yorodumi
- PDB-9hfs: Cryo-EM structure of human CDADC1 inactive mutant (E400A): hexame... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 9hfs
TitleCryo-EM structure of human CDADC1 inactive mutant (E400A): hexamer with dCTP bound in the active site
ComponentsCytidine and dCMP deaminase domain-containing protein 1
KeywordsHYDROLASE / Human dCTP deaminase / trimer / Zinc-dependent / Nucleotide metabolism
Function / homology
Function and homology information


dCMP deaminase activity / cytidine deaminase / : / DNA cytosine deamination / importin-alpha family protein binding / cytidine deaminase activity / protein homodimerization activity / zinc ion binding / nucleus / cytoplasm
Similarity search - Function
Deoxycytidylate deaminase domain / Deoxycytidylate deaminase-related / Cytidine and deoxycytidylate deaminase zinc-binding region / APOBEC/CMP deaminase, zinc-binding / Cytidine and deoxycytidylate deaminases zinc-binding region signature. / Cytidine and deoxycytidylate deaminase domain / Cytidine and deoxycytidylate deaminases domain profile. / Cytidine deaminase-like
Similarity search - Domain/homology
2'-DEOXYCYTIDINE-5'-TRIPHOSPHATE / Cytidine and dCMP deaminase domain-containing protein 1
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 2.8 Å
AuthorsSlyvka, A. / Rathore, I. / Yang, R. / Kanai, T. / Lountos, G. / Wang, Z. / Skowronek, K. / Czarnocki-Cieciura, M. / Wlodawer, A. / Bochtler, M.
Funding support Poland, United States, 4items
OrganizationGrant numberCountry
Foundation for Polish SciencePOIR.04.04.00-00-5D81/17-00 Poland
Ministry of Science and Higher Education (Poland)PPI/APM/2018/1/00034 Poland
National Institutes of Health/National Cancer Institute (NIH/NCI)NIH Intramural Research Program United States
National Institutes of Health/National Cancer Institute (NIH/NCI)75N91019D00024 United States
CitationJournal: Proc Natl Acad Sci U S A / Year: 2025
Title: Activity and structure of human (d)CTP deaminase CDADC1.
Authors: Anton Slyvka / Ishan Rathore / Renbin Yang / Olga Gewartowska / Tapan Kanai / George T Lountos / Krzysztof Skowronek / Mariusz Czarnocki-Cieciura / Alexander Wlodawer / Matthias Bochtler /
Abstract: Vertebrates have evolved an understudied protein termed CDADC1 (NYD-SP15) that contains an inactive N-terminal and active C-terminal DCTD-like domain. Here, we show that human CDADC1 is a (d)CTP- ...Vertebrates have evolved an understudied protein termed CDADC1 (NYD-SP15) that contains an inactive N-terminal and active C-terminal DCTD-like domain. Here, we show that human CDADC1 is a (d)CTP-specific deaminase, with a roughly 2-fold in vitro preference for dCTP over CTP. We determined high-resolution cryo-EM structures of CDADC1 in the absence of substrate and in complex with dCTP and 5-methyl-dCTP. The structures show that CDADC1 forms trimers and dimers of trimers in solution. The (d)CTP substrate is selected by a narrow pocket for the cytosine base and multiple lysine and arginine contacts to the triphosphate. Substrate binding promotes the association of trimers into hexamers and the transition of the hexamers from a loose to a tighter arrangement. Genetic experiments in mice show that loss of Cdadc1 is surprisingly well tolerated, even in the absence of the dCMP deaminase Dctd that is considered as the main source of dUMP, the precursor of dTTP.
History
DepositionNov 18, 2024Deposition site: PDBE / Processing site: PDBE
Revision 1.0Apr 30, 2025Provider: repository / Type: Initial release
Revision 1.1May 21, 2025Group: Data collection / Database references / Category: citation / citation_author / em_admin
Item: _citation.country / _citation.journal_abbrev ..._citation.country / _citation.journal_abbrev / _citation.journal_id_ASTM / _citation.journal_id_CSD / _citation.journal_id_ISSN / _citation.journal_volume / _citation.page_first / _citation.page_last / _citation.pdbx_database_id_DOI / _citation.pdbx_database_id_PubMed / _citation.title / _citation_author.identifier_ORCID / _citation_author.name / _em_admin.last_update

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Cytidine and dCMP deaminase domain-containing protein 1
B: Cytidine and dCMP deaminase domain-containing protein 1
C: Cytidine and dCMP deaminase domain-containing protein 1
D: Cytidine and dCMP deaminase domain-containing protein 1
E: Cytidine and dCMP deaminase domain-containing protein 1
F: Cytidine and dCMP deaminase domain-containing protein 1
hetero molecules


Theoretical massNumber of molelcules
Total (without water)367,50224
Polymers363,9146
Non-polymers3,58818
Water1086
1


  • Idetical with deposited unit
  • defined by author&software
  • Evidence: electron microscopy, gel filtration
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1

-
Components

#1: Protein
Cytidine and dCMP deaminase domain-containing protein 1 / Cytidine deaminase / Testis development protein NYD-SP15


Mass: 60652.320 Da / Num. of mol.: 6 / Mutation: E400A
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: CDADC1 / Production host: Escherichia coli BL21(DE3) (bacteria) / References: UniProt: Q9BWV3, cytidine deaminase
#2: Chemical
ChemComp-ZN / ZINC ION


Mass: 65.409 Da / Num. of mol.: 12 / Source method: obtained synthetically / Formula: Zn / Feature type: SUBJECT OF INVESTIGATION
#3: Chemical
ChemComp-DCP / 2'-DEOXYCYTIDINE-5'-TRIPHOSPHATE


Mass: 467.157 Da / Num. of mol.: 6 / Source method: obtained synthetically / Formula: C9H16N3O13P3 / Feature type: SUBJECT OF INVESTIGATION
#4: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 6 / Source method: isolated from a natural source / Formula: H2O
Has ligand of interestY
Has protein modificationN

-
Experimental details

-
Experiment

ExperimentMethod: ELECTRON MICROSCOPY
EM experimentAggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction

-
Sample preparation

ComponentName: Human CDADC1 hexamer with bound dCTP / Type: COMPLEX / Entity ID: #1 / Source: RECOMBINANT
Molecular weightValue: 0.363 MDa / Experimental value: YES
Source (natural)Organism: Homo sapiens (human)
Source (recombinant)Organism: Escherichia coli BL21(DE3) (bacteria)
Buffer solutionpH: 7.4
SpecimenConc.: 0.7 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES
Specimen supportGrid material: COPPER / Grid mesh size: 200 divisions/in. / Grid type: Quantifoil R1.2/1.3
VitrificationInstrument: FEI VITROBOT MARK IV / Cryogen name: ETHANE / Humidity: 100 % / Chamber temperature: 277.15 K

-
Electron microscopy imaging

Experimental equipment
Model: Talos Arctica / Image courtesy: FEI Company
MicroscopyModel: FEI TALOS ARCTICA
Electron gunElectron source: FIELD EMISSION GUN / Accelerating voltage: 200 kV / Illumination mode: FLOOD BEAM
Electron lensMode: BRIGHT FIELD / Nominal defocus max: 2500 nm / Nominal defocus min: 800 nm
Specimen holderCryogen: NITROGEN
Image recordingElectron dose: 42.6 e/Å2 / Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k)

-
Processing

EM software
IDNameCategory
1cryoSPARCparticle selection
2EPUimage acquisition
4cryoSPARCCTF correction
7UCSF ChimeraXmodel fitting
9PHENIXmodel refinement
10Cootmodel refinement
11cryoSPARCinitial Euler assignment
12cryoSPARCfinal Euler assignment
13cryoSPARCclassification
14cryoSPARC3D reconstruction
CTF correctionType: PHASE FLIPPING AND AMPLITUDE CORRECTION
SymmetryPoint symmetry: D3 (2x3 fold dihedral)
3D reconstructionResolution: 2.8 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 310460 / Symmetry type: POINT
Atomic model buildingProtocol: AB INITIO MODEL / Space: REAL
Atomic model buildingSource name: AlphaFold / Type: in silico model
RefinementCross valid method: NONE
Stereochemistry target values: GeoStd + Monomer Library + CDL v1.2
Displacement parametersBiso mean: 19.51 Å2
Refine LS restraints
Refine-IDTypeDev idealNumber
ELECTRON MICROSCOPYf_bond_d0.002218864
ELECTRON MICROSCOPYf_angle_d0.469625488
ELECTRON MICROSCOPYf_chiral_restr0.04032856
ELECTRON MICROSCOPYf_plane_restr0.00343192
ELECTRON MICROSCOPYf_dihedral_angle_d4.92172544

+
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