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- PDB-8u5i: Crystal Structure of human IDO1 bound to Compound 23 -

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Basic information

Entry
Database: PDB / ID: 8u5i
TitleCrystal Structure of human IDO1 bound to Compound 23
ComponentsIndoleamine 2,3-dioxygenase 1
KeywordsOXIDOREDUCTASE / IDO / TDO / complex
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 / 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 / : / Indoleamine 2,3-dioxygenase 1
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.17 Å
AuthorsSteinbacher, S. / Lammens, A. / Harris, S.F.
Funding support1items
OrganizationGrant numberCountry
Not funded
CitationJournal: To Be Published
Title: Exploiting Stereo-Complexity to Identify Spirocyclic Imidazoisoindoles as Potent and Orally Bioavailable Dual Inhibitors of Indoleamine-2,3-Dioxygenase and Tryptophan-2,3-Dioxygenase
Authors: Pastor, R. / Harris, S.F.
History
DepositionSep 12, 2023Deposition site: RCSB / Processing site: RCSB
Revision 1.0Nov 27, 2024Provider: repository / Type: Initial release

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Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

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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)90,7466
Polymers88,7102
Non-polymers2,0364
Water8,611478
1


  • Idetical with deposited unit
  • defined by author
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area4260 Å2
ΔGint-47 kcal/mol
Surface area31090 Å2
Unit cell
Length a, b, c (Å)84.862, 89.888, 133.520
Angle α, β, γ (deg.)90.00, 90.00, 90.00
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: 44355.102 Da / Num. of mol.: 2 / Fragment: N-TERMINAL TRUNCATED
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: IDO1, IDO, INDO / Production host: Escherichia coli (E. coli) / References: UniProt: P14902, indoleamine 2,3-dioxygenase
#2: Chemical ChemComp-HEM / PROTOPORPHYRIN IX CONTAINING FE / HEME


Mass: 616.487 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C34H32FeN4O4
#3: Chemical ChemComp-W2Z / (1R,2S)-8-(ethanesulfonyl)-2-[(4R,5S,9aM)-5H-imidazo[5,1-a]isoindol-5-yl]-8-azaspiro[4.5]decan-1-ol


Mass: 401.522 Da / Num. of mol.: 2 / Source method: isolated from a natural source / Formula: C21H27N3O3S / Feature type: SUBJECT OF INVESTIGATION
#4: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 478 / 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: 2.87 Å3/Da / Density % sol: 57.15 %
Crystal growTemperature: 293 K / Method: vapor diffusion, sitting drop / pH: 8 / Details: 20% (w/v) PEG 6K, 0.10M TRIS/HCl pH=8.0

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Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: SLS / Beamline: X10SA / Wavelength: 1 Å
DetectorType: DECTRIS PILATUS 6M / Detector: PIXEL / Date: Apr 7, 2017
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1 Å / Relative weight: 1
ReflectionResolution: 2.17→45.31 Å / Num. obs: 53451 / % possible obs: 97.7 % / Redundancy: 5.6 % / CC1/2: 0.999 / Rmerge(I) obs: 0.071 / Rrim(I) all: 0.078 / Net I/σ(I): 17.71
Reflection shell
Resolution (Å)Rmerge(I) obsNum. unique obsCC1/2Rrim(I) allDiffraction-ID
2.17-2.420.443148860.9330.4871
2.42-2.670.24298320.9720.2661
2.67-3.070.12297890.9910.1351
3.07-3.740.05785210.9970.0631
3.74-4.740.03352700.9980.0371
4.74-6.080.02926930.9990.0321
6.08-8.880.02616440.9990.0281
8.88-14.210.0216130.9990.0231
14.21-45.310.0252030.9980.0281

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Processing

Software
NameVersionClassification
REFMAC5.2.0005refinement
XDSdata reduction
XSCALEdata scaling
PHASERphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT / Resolution: 2.17→45.31 Å / Cor.coef. Fo:Fc: 0.955 / Cor.coef. Fo:Fc free: 0.929 / SU B: 8.722 / SU ML: 0.125 / Cross valid method: THROUGHOUT / ESU R: 0.2 / ESU R Free: 0.173 / Stereochemistry target values: MAXIMUM LIKELIHOOD / Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS
RfactorNum. reflection% reflectionSelection details
Rfree0.21923 1459 2.7 %RANDOM
Rwork0.17679 ---
obs0.17795 51992 97.67 %-
Solvent computationIon probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å / Solvent model: BABINET MODEL WITH MASK
Displacement parametersBiso mean: 38.619 Å2
Baniso -1Baniso -2Baniso -3
1--2.04 Å20 Å20 Å2
2--0.54 Å20 Å2
3---1.5 Å2
Refinement stepCycle: LAST / Resolution: 2.17→45.31 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms5953 0 142 478 6573
Refine LS restraints
Refine-IDTypeDev idealDev ideal targetNumber
X-RAY DIFFRACTIONr_bond_refined_d0.010.0226364
X-RAY DIFFRACTIONr_bond_other_d0.0020.025755
X-RAY DIFFRACTIONr_angle_refined_deg1.2122.0168706
X-RAY DIFFRACTIONr_angle_other_deg0.973313361
X-RAY DIFFRACTIONr_dihedral_angle_1_deg5.4655791
X-RAY DIFFRACTIONr_dihedral_angle_2_deg34.03424.161274
X-RAY DIFFRACTIONr_dihedral_angle_3_deg12.463151044
X-RAY DIFFRACTIONr_dihedral_angle_4_deg15.0981533
X-RAY DIFFRACTIONr_chiral_restr0.0710.2940
X-RAY DIFFRACTIONr_gen_planes_refined0.0040.027146
X-RAY DIFFRACTIONr_gen_planes_other0.0010.021275
X-RAY DIFFRACTIONr_nbd_refined0.1870.21403
X-RAY DIFFRACTIONr_nbd_other0.1410.25753
X-RAY DIFFRACTIONr_nbtor_refined0.1620.23103
X-RAY DIFFRACTIONr_nbtor_other0.0760.23198
X-RAY DIFFRACTIONr_xyhbond_nbd_refined0.1120.2429
X-RAY DIFFRACTIONr_xyhbond_nbd_other
X-RAY DIFFRACTIONr_metal_ion_refined
X-RAY DIFFRACTIONr_metal_ion_other
X-RAY DIFFRACTIONr_symmetry_vdw_refined0.1920.216
X-RAY DIFFRACTIONr_symmetry_vdw_other0.1370.248
X-RAY DIFFRACTIONr_symmetry_hbond_refined0.1020.216
X-RAY DIFFRACTIONr_symmetry_hbond_other
X-RAY DIFFRACTIONr_symmetry_metal_ion_refined
X-RAY DIFFRACTIONr_symmetry_metal_ion_other
X-RAY DIFFRACTIONr_mcbond_it1.62125043
X-RAY DIFFRACTIONr_mcbond_other0.35521559
X-RAY DIFFRACTIONr_mcangle_it1.98436264
X-RAY DIFFRACTIONr_mcangle_other
X-RAY DIFFRACTIONr_scbond_it3.12842939
X-RAY DIFFRACTIONr_scbond_other
X-RAY DIFFRACTIONr_scangle_it4.16462438
X-RAY DIFFRACTIONr_scangle_other
X-RAY DIFFRACTIONr_long_range_B_refined
X-RAY DIFFRACTIONr_long_range_B_other
X-RAY DIFFRACTIONr_rigid_bond_restr
X-RAY DIFFRACTIONr_sphericity_free
X-RAY DIFFRACTIONr_sphericity_bonded
LS refinement shellResolution: 2.17→2.226 Å / Total num. of bins used: 20
RfactorNum. reflection% reflection
Rfree0.272 110 -
Rwork0.221 3819 -
obs--98.55 %
Refinement TLS params.

Method: refined / Refine-ID: X-RAY DIFFRACTION

IDL11 (°2)L12 (°2)L13 (°2)L22 (°2)L23 (°2)L33 (°2)S11 (Å °)S12 (Å °)S13 (Å °)S21 (Å °)S22 (Å °)S23 (Å °)S31 (Å °)S32 (Å °)S33 (Å °)T11 (Å2)T12 (Å2)T13 (Å2)T22 (Å2)T23 (Å2)T33 (Å2)Origin x (Å)Origin y (Å)Origin z (Å)
13.53381.2484-1.35933.0714-1.44164.24860.0163-0.3532-0.30280.075-0.2206-0.52750.06760.69120.2044-0.1202-0.0203-0.03940.0372-0.00360.00660.49-0.542-18.819
22.7120.2867-0.92551.4236-0.23681.6139-0.0144-0.2559-0.06080.1948-0.06270.08990.03350.12060.0771-0.0815-0.0284-0.0115-0.0887-0.0053-0.1056-18.66-0.485-12.825
34.93992.7221-0.54376.589-3.21165.0490.03220.08870.22480.06370.04160.40450.0646-0.2445-0.0739-0.12780.0293-0.0223-0.1569-0.0277-0.0778-30.0487.477-20.288
44.1696-0.38821.32952.4189-0.07642.1523-0.0784-0.32110.1666-0.012-0.00810.2425-0.054-0.19130.0866-0.1347-0.00210.0203-0.1623-0.0385-0.0175-46.526-22.891-27.567
53.3114-0.88891.00151.3019-0.13091.1047-0.057-0.10420.07930.0848-0.0188-0.05630.05390.06650.0757-0.0897-0.00050.0253-0.1342-0.0151-0.1097-27.525-28.251-24.02
64.71850.2633.00932.90070.72026.80550.04190.6028-0.0056-0.2665-0.1282-0.2336-0.02770.49890.0863-0.10030.02960.0837-0.0456-0.014-0.0962-16.928-31-35.56
Refinement TLS group
IDRefine-IDRefine TLS-IDAuth asym-IDAuth seq-ID
1X-RAY DIFFRACTION1A1 - 107
2X-RAY DIFFRACTION2A108 - 335
3X-RAY DIFFRACTION3A336 - 403
4X-RAY DIFFRACTION4B1 - 107
5X-RAY DIFFRACTION5B108 - 335
6X-RAY DIFFRACTION6B336 - 403

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