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- PDB-7e0p: Crystal Structure of Human Indoleamine 2,3-dioxygenagse 1 (hIDO1)... -

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Basic information

Entry
Database: PDB / ID: 7e0p
TitleCrystal Structure of Human Indoleamine 2,3-dioxygenagse 1 (hIDO1) Complexed with 4-(((6-Bromo-1H-indazol-4-yl)amino)methyl)phenol (2)
ComponentsIndoleamine 2,3-dioxygenase 1
KeywordsOXIDOREDUCTASE / Indoleamine 2 / 3-dioxygenase 1
Function / homology
Function and homology information


indoleamine 2,3-dioxygenase / positive regulation of chronic inflammatory response / indoleamine 2,3-dioxygenase activity / kynurenic acid biosynthetic process / smooth muscle contractile fiber / 'de novo' NAD+ biosynthetic process from L-tryptophan / L-tryptophan 2,3-dioxygenase activity / positive regulation of T cell tolerance induction / L-tryptophan catabolic process to kynurenine / quinolinate biosynthetic process ... indoleamine 2,3-dioxygenase / positive regulation of chronic inflammatory response / indoleamine 2,3-dioxygenase activity / kynurenic acid biosynthetic process / smooth muscle contractile fiber / 'de novo' NAD+ biosynthetic process from L-tryptophan / L-tryptophan 2,3-dioxygenase activity / positive regulation of T cell tolerance induction / L-tryptophan catabolic process to kynurenine / quinolinate biosynthetic process / stereocilium bundle / positive regulation of type 2 immune response / L-tryptophan catabolic process / Tryptophan catabolism / negative regulation of T cell apoptotic process / positive 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 / cytoplasm / cytosol
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
ACETIC ACID / PROTOPORPHYRIN IX CONTAINING FE / Chem-HU0 / Indoleamine 2,3-dioxygenase 1
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.635 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
Revision 1.2Oct 16, 2024Group: Structure summary / Category: pdbx_entry_details / pdbx_modification_feature / Item: _pdbx_entry_details.has_protein_modification

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Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

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Assembly

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


Theoretical massNumber of molelcules
Total (without water)90,1517
Polymers88,2222
Non-polymers1,9295
Water1448
1
A: Indoleamine 2,3-dioxygenase 1
hetero molecules


Theoretical massNumber of molelcules
Total (without water)45,0453
Polymers44,1111
Non-polymers9352
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area1190 Å2
ΔGint-22 kcal/mol
Surface area15970 Å2
MethodPISA
2
B: Indoleamine 2,3-dioxygenase 1
hetero molecules


Theoretical massNumber of molelcules
Total (without water)45,1054
Polymers44,1111
Non-polymers9953
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area1200 Å2
ΔGint-23 kcal/mol
Surface area16170 Å2
MethodPISA
Unit cell
Length a, b, c (Å)85.746, 91.561, 126.767
Angle α, β, γ (deg.)90.000, 90.000, 90.000
Int Tables number19
Space group name H-MP212121

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Components

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


Mass: 44110.754 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-HU0 / 4-[[(6-bromanyl-1~{H}-indazol-4-yl)amino]methyl]phenol


Mass: 318.169 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C14H12BrN3O / Feature type: SUBJECT OF INVESTIGATION
#3: Chemical ChemComp-HEM / PROTOPORPHYRIN IX CONTAINING FE / HEME


Mass: 616.487 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C34H32FeN4O4 / Feature type: SUBJECT OF INVESTIGATION
#4: Chemical ChemComp-ACY / ACETIC ACID


Mass: 60.052 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C2H4O2
#5: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 8 / Source method: isolated from a natural source / Formula: H2O
Has ligand of interestY
Has protein modificationY

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Experimental details

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Experiment

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

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Sample preparation

CrystalDensity Matthews: 2.82 Å3/Da / Density % sol: 56.39 %
Crystal growTemperature: 293 K / Method: vapor diffusion, hanging drop / Details: 15% to 23% PEG 8000, 0.2M ammonium acetate

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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: 2.63→71.02 Å / Num. obs: 29740 / % possible obs: 98.3 % / Redundancy: 13.1 % / Biso Wilson estimate: 64.46 Å2 / CC1/2: 1 / Rmerge(I) obs: 0.078 / Rpim(I) all: 0.022 / Rrim(I) all: 0.081 / Net I/σ(I): 23.9 / Num. measured all: 389915 / Scaling rejects: 5
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
2.63-2.7812.80.9124972038900.8920.2610.952.989.1
8.33-71.0210.20.02210744105410.0070.02365.498.6

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Processing

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

5etw


Resolution: 2.635→63.383 Å / SU ML: 0.42 / Cross valid method: THROUGHOUT / σ(F): 1.35 / Phase error: 31.83 / Stereochemistry target values: ML
RfactorNum. reflection% reflection
Rfree0.266 1997 6.73 %
Rwork0.1999 27656 -
obs0.2043 29653 98.22 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL
Displacement parametersBiso max: 150.99 Å2 / Biso mean: 74.285 Å2 / Biso min: 35.89 Å2
Refinement stepCycle: final / Resolution: 2.635→63.383 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms5876 0 128 8 6012
Biso mean--65.49 58.37 -
Num. residues----742
Refine LS restraints
Refine-IDTypeDev idealNumber
X-RAY DIFFRACTIONf_bond_d0.0176179
X-RAY DIFFRACTIONf_angle_d1.4698381
X-RAY DIFFRACTIONf_chiral_restr0.06902
X-RAY DIFFRACTIONf_plane_restr0.0091061
X-RAY DIFFRACTIONf_dihedral_angle_d17.8333653
LS refinement shell

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

Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection Rwork% reflection obs (%)
2.635-2.70070.43261150.347156078
2.7007-2.77370.34191340.29971978100
2.7737-2.85530.34071540.27411967100
2.8553-2.94750.33931480.27761974100
2.9475-3.05280.34611270.27942000100
3.0528-3.17510.35651530.27651972100
3.1751-3.31960.31851450.26671980100
3.3196-3.49460.34181390.2411991100
3.4946-3.71350.27231410.22332010100
3.7135-4.00020.25471460.18772002100
4.0002-4.40260.22551490.17382009100
4.4026-5.03950.24041460.16352044100
5.0395-6.34830.24731470.17762049100
6.3483-63.3830.20421530.1446212098

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