[English] 日本語
Yorodumi
- PDB-9ccc: Crystal structure of human dihydroorotate dehydrogenase with new ... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 9ccc
TitleCrystal structure of human dihydroorotate dehydrogenase with new alkyne ligand
ComponentsDihydroorotate dehydrogenase (quinone), mitochondrial
KeywordsOXIDOREDUCTASE / Human DHODH / inhibitor / antiviral / alkyne
Function / homology
Function and homology information


pyrimidine ribonucleotide biosynthetic process / dihydroorotate dehydrogenase (quinone) / dihydroorotate dehydrogenase (quinone) activity / dihydroorotate dehydrogenase activity / dihydroorotase activity / Pyrimidine biosynthesis / UDP biosynthetic process / 'de novo' UMP biosynthetic process / 'de novo' pyrimidine nucleobase biosynthetic process / mitochondrial inner membrane ...pyrimidine ribonucleotide biosynthetic process / dihydroorotate dehydrogenase (quinone) / dihydroorotate dehydrogenase (quinone) activity / dihydroorotate dehydrogenase activity / dihydroorotase activity / Pyrimidine biosynthesis / UDP biosynthetic process / 'de novo' UMP biosynthetic process / 'de novo' pyrimidine nucleobase biosynthetic process / mitochondrial inner membrane / mitochondrion / nucleoplasm / cytosol
Similarity search - Function
Dihydroorotate dehydrogenase, class 2 / Dihydroorotate dehydrogenase signature 1. / Dihydroorotate dehydrogenase signature 2. / Dihydroorotate dehydrogenase, conserved site / : / Dihydroorotate dehydrogenase domain / Dihydroorotate dehydrogenase / Aldolase-type TIM barrel
Similarity search - Domain/homology
: / FLAVIN MONONUCLEOTIDE / OROTIC ACID / Dihydroorotate dehydrogenase (quinone), mitochondrial
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2 Å
AuthorsPurificacao, A.D. / Andrade, C.H. / Emery, F.S. / Nonato, M.C.
Funding support Brazil, 3items
OrganizationGrant numberCountry
Brazilian National Council for Scientific and Technological Development (CNPq)441038/2020-4 Brazil
Sao Paulo Research Foundation (FAPESP)2020/06190-0 Brazil
Sao Paulo Research Foundation (FAPESP)2021/13237-5 Brazil
CitationJournal: To Be Published
Title: Discovery of a novel alkyne-based scaffold inhibitor for human DHODH.
Authors: Purificacao, A.D. / Vaidergorn, M.M. / Silva-Mendonca, S. / Silva, W.J.L. / Leite, P.I.P. / Santos, T. / Andrade, C.H. / Nonato, M.C. / Emery, F.S.
History
DepositionJun 21, 2024Deposition site: RCSB / Processing site: RCSB
Revision 1.0Jun 25, 2025Provider: repository / Type: Initial release

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Dihydroorotate dehydrogenase (quinone), mitochondrial
hetero molecules


Theoretical massNumber of molelcules
Total (without water)41,31010
Polymers39,9441
Non-polymers1,3679
Water4,684260
1


  • Idetical with deposited unit
  • defined by author
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Unit cell
Length a, b, c (Å)91.042, 91.042, 122.616
Angle α, β, γ (deg.)90.000, 90.000, 120.000
Int Tables number154
Space group name H-MP3221
Space group name HallP322"
Symmetry operation#1: x,y,z
#2: -y,x-y,z+2/3
#3: -x+y,-x,z+1/3
#4: x-y,-y,-z+1/3
#5: -x,-x+y,-z+2/3
#6: y,x,-z

-
Components

-
Protein , 1 types, 1 molecules A

#1: Protein Dihydroorotate dehydrogenase (quinone), mitochondrial / DHOdehase / Dihydroorotate oxidase


Mass: 39943.613 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: DHODH / Production host: Escherichia coli (E. coli)
References: UniProt: Q02127, dihydroorotate dehydrogenase (quinone)

-
Non-polymers , 7 types, 269 molecules

#2: Chemical ChemComp-ORO / OROTIC ACID


Mass: 156.096 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C5H4N2O4 / Feature type: SUBJECT OF INVESTIGATION
#3: Chemical ChemComp-A1AVV / N-{4-[(3-aminophenyl)ethynyl]phenyl}acetamide


Mass: 250.295 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C16H14N2O / Feature type: SUBJECT OF INVESTIGATION
#4: Chemical ChemComp-SO4 / SULFATE ION


Mass: 96.063 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: SO4
#5: Chemical ChemComp-GOL / GLYCEROL / GLYCERIN / PROPANE-1,2,3-TRIOL


Mass: 92.094 Da / Num. of mol.: 3 / Source method: obtained synthetically / Formula: C3H8O3
#6: Chemical ChemComp-CL / CHLORIDE ION


Mass: 35.453 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: Cl
#7: Chemical ChemComp-FMN / FLAVIN MONONUCLEOTIDE / RIBOFLAVIN MONOPHOSPHATE


Mass: 456.344 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C17H21N4O9P / Feature type: SUBJECT OF INVESTIGATION
#8: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 260 / Source method: isolated from a natural source / Formula: H2O

-
Details

Has ligand of interestY
Has protein modificationN

-
Experimental details

-
Experiment

ExperimentMethod: X-RAY DIFFRACTION / Number of used crystals: 1

-
Sample preparation

CrystalDensity Matthews: 3.79 Å3/Da / Density % sol: 67.54 % / Description: Yellow square crystals
Crystal growTemperature: 294.15 K / Method: vapor diffusion, sitting drop / pH: 4.8
Details: 0.1 M sodium acetate trihydrate pH 4.8 2 M ammonium sulfate 30% (v/v) glycerol

-
Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: LNLS SIRIUS / Beamline: MANACA / Wavelength: 0.97718 Å
DetectorType: DECTRIS PILATUS 2M / Detector: PIXEL / Date: Dec 2, 2022
RadiationMonochromator: M / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.97718 Å / Relative weight: 1
ReflectionResolution: 2→48.4 Å / Num. obs: 40306 / % possible obs: 99.9 % / Observed criterion σ(I): 1 / Redundancy: 14.2 % / Biso Wilson estimate: 17.27 Å2 / CC1/2: 0.984 / CC star: 0.996 / Net I/σ(I): 8.41
Reflection shellResolution: 2→2.05 Å / Mean I/σ(I) obs: 1.7 / Num. unique obs: 2945 / CC1/2: 0.321 / CC star: 0.877 / % possible all: 84.13

-
Processing

Software
NameVersionClassification
PHENIX1.14_3260refinement
XDSJan 10, 2022 BUILT=20220220data reduction
AimlessVersion 0.7.9data scaling
pointlessVersion 1.12.14data scaling
PHASER2.8.2phasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT / Resolution: 2→48.4 Å / SU ML: 0.2443 / Cross valid method: FREE R-VALUE / σ(F): 1.33 / Phase error: 27.7696 / Stereochemistry target values: CDL v1.2
RfactorNum. reflection% reflection
Rfree0.2732 1834 4.99 %
Rwork0.2397 34943 -
obs0.2413 36777 91.24 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL
Displacement parametersBiso mean: 20.08 Å2
Refinement stepCycle: LAST / Resolution: 2→48.4 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms2688 0 90 260 3038
Refine LS restraints
Refine-IDTypeDev idealNumber
X-RAY DIFFRACTIONf_bond_d0.0122868
X-RAY DIFFRACTIONf_angle_d1.3023887
X-RAY DIFFRACTIONf_chiral_restr0.0717432
X-RAY DIFFRACTIONf_plane_restr0.0104506
X-RAY DIFFRACTIONf_dihedral_angle_d17.87061050
LS refinement shell
Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkRefine-ID% reflection obs (%)
2-2.050.35131340.30422445X-RAY DIFFRACTION84.09
2.05-2.110.31581320.29432380X-RAY DIFFRACTION81.58
2.11-2.180.2411310.23412545X-RAY DIFFRACTION87.74
2.18-2.260.26431320.22382646X-RAY DIFFRACTION90.84
2.26-2.350.24341410.20912645X-RAY DIFFRACTION90.31
2.35-2.460.27241370.21972699X-RAY DIFFRACTION92.41
2.46-2.590.27961410.21172708X-RAY DIFFRACTION93.23
2.59-2.750.24671350.21872654X-RAY DIFFRACTION90.26
2.75-2.960.28261360.21592694X-RAY DIFFRACTION92.21
2.96-3.260.27561530.22132763X-RAY DIFFRACTION93.43
3.26-3.730.26151520.22522851X-RAY DIFFRACTION96.16
3.73-4.70.23181550.23992901X-RAY DIFFRACTION97.39
4.7-48.40.32031550.28833012X-RAY DIFFRACTION96

+
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