[English] 日本語
Yorodumi
- PDB-7e0u: Crystal Structure of Human Indoleamine 2,3-dioxygenagse 1 (hIDO1)... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 7e0u
TitleCrystal Structure of Human Indoleamine 2,3-dioxygenagse 1 (hIDO1) Complexed with 6-Bromo-N-(((1S,2S)-2-chlorocyclohexyl)methyl)-1H-indazol-4-amine (39)
ComponentsIndoleamine 2,3-dioxygenase 1
KeywordsOXIDOREDUCTASE / Indoleamine 2 / 3-dioxygenase 1
Function / homology
Function and homology information


indoleamine 2,3-dioxygenase / smooth muscle contractile fiber / indoleamine 2,3-dioxygenase activity / positive regulation of chronic inflammatory response / kynurenic acid biosynthetic process / tryptophan 2,3-dioxygenase activity / positive regulation of T cell tolerance induction / tryptophan catabolic process to kynurenine / stereocilium bundle / positive regulation of type 2 immune response ... indoleamine 2,3-dioxygenase / smooth muscle contractile fiber / indoleamine 2,3-dioxygenase activity / positive regulation of chronic inflammatory response / kynurenic acid biosynthetic process / tryptophan 2,3-dioxygenase activity / positive regulation of T cell tolerance induction / tryptophan catabolic process to kynurenine / stereocilium bundle / positive regulation of type 2 immune response / 'de novo' NAD biosynthetic process from tryptophan / tryptophan catabolic process / Tryptophan catabolism / positive regulation of T cell apoptotic process / negative regulation of T cell apoptotic process / swimming behavior / negative regulation of interleukin-10 production / multicellular organismal response to stress / T cell proliferation / negative regulation of T cell proliferation / positive regulation of interleukin-12 production / female pregnancy / response to lipopolysaccharide / electron transfer activity / inflammatory response / heme binding / metal ion binding / cytosol / cytoplasm
Similarity search - Function
Indoleamine 2,3-dioxygenase / Indoleamine 2,3-dioxygenase / Indoleamine 2,3-dioxygenase signature 1. / Indoleamine 2,3-dioxygenase signature 2. / Tryptophan/Indoleamine 2,3-dioxygenase-like
Similarity search - Domain/homology
PROTOPORPHYRIN IX CONTAINING FE / Chem-HUC / Indoleamine 2,3-dioxygenase 1
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.278 Å
AuthorsLi, G.-B. / Ning, X.-L.
Funding support China, 1items
OrganizationGrant numberCountry
National Natural Science Foundation of China (NSFC)81874291;81502989; 82073698 China
CitationJournal: J.Med.Chem. / Year: 2021
Title: X-ray Structure-Guided Discovery of a Potent, Orally Bioavailable, Dual Human Indoleamine/Tryptophan 2,3-Dioxygenase (hIDO/hTDO) Inhibitor That Shows Activity in a Mouse Model of Parkinson's Disease.
Authors: Ning, X.L. / Li, Y.Z. / Huo, C. / Deng, J. / Gao, C. / Zhu, K.R. / Wang, M. / Wu, Y.X. / Yu, J.L. / Ren, Y.L. / Luo, Z.Y. / Li, G. / Chen, Y. / Wang, S.Y. / Peng, C. / Yang, L.L. / Wang, Z.Y. ...Authors: Ning, X.L. / Li, Y.Z. / Huo, C. / Deng, J. / Gao, C. / Zhu, K.R. / Wang, M. / Wu, Y.X. / Yu, J.L. / Ren, Y.L. / Luo, Z.Y. / Li, G. / Chen, Y. / Wang, S.Y. / Peng, C. / Yang, L.L. / Wang, Z.Y. / Wu, Y. / Qian, S. / Li, G.B.
History
DepositionJan 28, 2021Deposition site: PDBJ / Processing site: PDBJ
Revision 1.0Jul 21, 2021Provider: repository / Type: Initial release
Revision 1.1Nov 29, 2023Group: Data collection / Database references / Refinement description
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / database_2 / pdbx_initial_refinement_model
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Indoleamine 2,3-dioxygenase 1
B: Indoleamine 2,3-dioxygenase 1
hetero molecules


Theoretical massNumber of molelcules
Total (without water)90,1726
Polymers88,2532
Non-polymers1,9184
Water1,946108
1
A: Indoleamine 2,3-dioxygenase 1
hetero molecules


Theoretical massNumber of molelcules
Total (without water)45,0863
Polymers44,1271
Non-polymers9592
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area1220 Å2
ΔGint-23 kcal/mol
Surface area16360 Å2
MethodPISA
2
B: Indoleamine 2,3-dioxygenase 1
hetero molecules


Theoretical massNumber of molelcules
Total (without water)45,0863
Polymers44,1271
Non-polymers9592
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area1210 Å2
ΔGint-23 kcal/mol
Surface area16250 Å2
MethodPISA
Unit cell
Length a, b, c (Å)85.487, 91.503, 128.074
Angle α, β, γ (deg.)90.000, 90.000, 90.000
Int Tables number19
Space group name H-MP212121

-
Components

#1: Protein Indoleamine 2,3-dioxygenase 1 / / IDO-1 / Indoleamine-pyrrole 2 / 3-dioxygenase


Mass: 44126.711 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: IDO1, IDO, INDO / Production host: Escherichia coli BL21(DE3) (bacteria) / References: UniProt: P14902, indoleamine 2,3-dioxygenase
#2: Chemical ChemComp-HEM / PROTOPORPHYRIN IX CONTAINING FE / HEME / Heme B


Mass: 616.487 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C34H32FeN4O4 / Feature type: SUBJECT OF INVESTIGATION
#3: Chemical ChemComp-HUC / 6-bromanyl-~{N}-[[(1~{S},2~{S})-2-chloranylcyclohexyl]methyl]-1~{H}-indazol-4-amine


Mass: 342.662 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C14H17BrClN3 / Feature type: SUBJECT OF INVESTIGATION
#4: Water ChemComp-HOH / water / Water


Mass: 18.015 Da / Num. of mol.: 108 / Source method: isolated from a natural source / Formula: H2O
Has ligand of interestY

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 2.84 Å3/Da / Density % sol: 56.67 %
Crystal growTemperature: 293 K / Method: vapor diffusion, hanging drop / Details: 15% to 23% PEG 8000, 0.2M ammonium acetate

-
Data collection

DiffractionMean temperature: 195 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: SSRF / Beamline: BL19U1 / Wavelength: 0.97918 Å
DetectorType: DECTRIS PILATUS3 X CdTe 1M / Detector: PIXEL / Date: Oct 29, 2020
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.97918 Å / Relative weight: 1
ReflectionResolution: 2.278→74.453 Å / Num. obs: 46598 / % possible obs: 99.8 % / Redundancy: 12.9 % / Biso Wilson estimate: 53.42 Å2 / CC1/2: 0.999 / Rmerge(I) obs: 0.078 / Rpim(I) all: 0.023 / Rrim(I) all: 0.081 / Net I/σ(I): 19
Reflection shell

Diffraction-ID: 1

Resolution (Å)Redundancy (%)Rmerge(I) obsNum. measured allNum. unique obsCC1/2Rpim(I) allRrim(I) allNet I/σ(I) obs% possible all
2.28-2.413.40.9898960766910.9060.2791.0282.699.9
7.2-74.4510.80.0381752216250.9990.0120.0449.399.6

-
Processing

Software
NameVersionClassification
Aimless0.7.4data scaling
PHENIX1.10.1_2155refinement
PDB_EXTRACT3.27data extraction
AutoProcessdata reduction
PHASERphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 5etw

5etw


Resolution: 2.278→74.453 Å / SU ML: 0.28 / Cross valid method: THROUGHOUT / σ(F): 1.35 / Phase error: 28.07 / Stereochemistry target values: ML
RfactorNum. reflection% reflection
Rfree0.2482 1997 4.3 %
Rwork0.1897 44473 -
obs0.1921 46470 99.61 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL
Displacement parametersBiso max: 128.5 Å2 / Biso mean: 63.9333 Å2 / Biso min: 34.72 Å2
Refinement stepCycle: final / Resolution: 2.278→74.453 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms6004 0 124 108 6236
Biso mean--47.29 55.9 -
Num. residues----760
Refine LS restraints
Refine-IDTypeDev idealNumber
X-RAY DIFFRACTIONf_bond_d0.0156329
X-RAY DIFFRACTIONf_angle_d1.3128588
X-RAY DIFFRACTIONf_chiral_restr0.062926
X-RAY DIFFRACTIONf_plane_restr0.0091090
X-RAY DIFFRACTIONf_dihedral_angle_d17.1773763
LS refinement shell

Refine-ID: X-RAY DIFFRACTION / Rfactor Rfree error: 0

Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection Rwork% reflection obs (%)
2.278-2.33470.32081410.26073103100
2.3347-2.39780.29711380.24893154100
2.3978-2.46840.33971370.25313142100
2.4684-2.5480.29381530.23943146100
2.548-2.63910.2421270.2353152100
2.6391-2.74480.34691530.23923146100
2.7448-2.86970.32481410.24213176100
2.8697-3.0210.33961470.24013164100
3.021-3.21030.31421420.24133178100
3.2103-3.45810.26281380.22613182100
3.4581-3.80610.2531500.19863205100
3.8061-4.35680.23571330.166313297
4.3568-5.48890.21231430.14813251100
5.4889-74.4530.17621540.1428334298

+
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