PDB-8vzv: Human TDO (hTDO) in complex with LM10

ID or keywords:

Entry

Database: PDB / ID: 8vzv

Title

Human TDO (hTDO) in complex with LM10

Components

Tryptophan 2,3-dioxygenase

Keywords

CYTOSOLIC PROTEIN / Human TDO / hTDO / LM10

Function / homology

Function and homology information

response to nitroglycerin / tryptophan catabolic process to acetyl-CoA / tryptophan 2,3-dioxygenase / tryptophan 2,3-dioxygenase activity / tryptophan catabolic process to kynurenine / Tryptophan catabolism / amino acid binding / oxygen binding / protein homotetramerization / heme binding ...
Similarity search - Function

Biological species

Homo sapiens (human)

Method

X-RAY DIFFRACTION /

SYNCHROTRON /

MOLECULAR REPLACEMENT / Resolution: 2.29 Å

Authors

Ishigami, I. / Yeh, S.-R. / Lewis-Ballester, A.

Funding support

United States, 2items

Organization	Grant number	Country
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)	GM115773	United States
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)	GM151419	United States

Citation

Journal: J.Med.Chem. / Year: 2024
Title: Structural Insights into Protein-Inhibitor Interactions in Human Tryptophan Dioxygenase.
Authors: Geeraerts, Z. / Ishigami, I. / Lewis-Ballester, A. / Pham, K.N. / Kozlova, A. / Mathieu, C. / Frederick, R. / Yeh, S.R.

History

Deposition	Feb 12, 2024	Deposition site: RCSB / Processing site: RCSB
Revision 1.0	Aug 28, 2024	Provider: repository / Type: Initial release
Revision 1.1	Sep 4, 2024	Group: Database references / Category: citation Item: _citation.journal_volume / _citation.page_first / _citation.page_last
Revision 1.2	Sep 11, 2024	Group: Database references / Category: citation_author / Item: _citation_author.identifier_ORCID

Structure viewer	Molecule: MolmilJmol/JSmol

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PDBx/mmCIF format	8vzv.cif.gz	317.1 KB	Display	PDBx/mmCIF format
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Validation report

Summary document	8vzv_validation.pdf.gz	3.7 MB	Display	wwPDB validaton report
Full document	8vzv_full_validation.pdf.gz	3.7 MB	Display
Data in XML	8vzv_validation.xml.gz	54.1 KB	Display
Data in CIF	8vzv_validation.cif.gz	71.3 KB	Display
Arichive directory	https://data.pdbj.org/pub/pdb/validation_reports/vz/8vzv ftp://data.pdbj.org/pub/pdb/validation_reports/vz/8vzv	HTTPS FTP

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Related structure data

Related structure data	7lu7C 8vtqC 8vugC 8w1hC 8w2kC 9at2C 9b17C 9b1qC C: citing same article (ref.)
Similar structure data	Similarity search - Function & homologyF&H Search Similarity search - FunctionF&H Search Similarity search - HomologyF&H Search

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Links

PDB pages	PDBj / wwPDB / NCBI

Deposited unit

AAA: Tryptophan 2,3-dioxygenase

BBB: Tryptophan 2,3-dioxygenase

CCC: Tryptophan 2,3-dioxygenase

DDD: Tryptophan 2,3-dioxygenase

hetero molecules

185 kDa, 4 polymers
Search similar-shape structures of this assembly by Omokage search (details)

1

Idetical with deposited unit
defined by author&software

Unit cell

Length a, b, c (Å)	143.428, 152.919, 87.588
Angle α, β, γ (deg.)	90.000, 90.000, 90.000
Int Tables number	18
Space group name H-M	P2₁2₁2

Noncrystallographic symmetry (NCS)

NCS domain:

ID	Ens-ID	Details
1	1	AAA
2	1	BBB
3	2	AAA
4	2	CCC
5	3	AAA
6	3	DDD
7	4	BBB
8	4	CCC
9	5	BBB
10	5	DDD
11	6	CCC
12	6	DDD

NCS domain segments:

Beg auth comp-ID: GLY / Beg label comp-ID: GLY

Dom-ID	Component-ID	Ens-ID	End auth comp-ID	End label comp-ID	Auth asym-ID	Label asym-ID	Auth seq-ID	Label seq-ID
1	1	1	LEU	LEU	AAA	A	39 - 389	23 - 373
2	2	1	LEU	LEU	BBB	B	39 - 389	23 - 373
3	1	2	HIS	HIS	AAA	A	39 - 391	23 - 375
4	2	2	HIS	HIS	CCC	C	39 - 391	23 - 375
5	1	3	GLU	GLU	AAA	A	39 - 390	23 - 374
6	2	3	GLU	GLU	DDD	D	39 - 390	23 - 374
7	1	4	LEU	LEU	BBB	B	39 - 389	23 - 373
8	2	4	LEU	LEU	CCC	C	39 - 389	23 - 373
9	1	5	LEU	LEU	BBB	B	39 - 389	23 - 373
10	2	5	LEU	LEU	DDD	D	39 - 389	23 - 373
11	1	6	GLU	GLU	CCC	C	39 - 390	23 - 374
12	2	6	GLU	GLU	DDD	D	39 - 390	23 - 374

NCS ensembles :

ID	Details
1	Local NCS retraints between domains: 1 2
2	Local NCS retraints between domains: 3 4
3	Local NCS retraints between domains: 5 6
4	Local NCS retraints between domains: 7 8
5	Local NCS retraints between domains: 9 10
6	Local NCS retraints between domains: 11 12

#1: Protein	Tryptophan 2,3-dioxygenase / TDO / Tryptamin 2 / 3-dioxygenase / Tryptophan oxygenase / TRPO / Tryptophan pyrrolase / Tryptophanase Mass: 45182.535 Da / Num. of mol.: 4 / Fragment: UNP residues 18-389 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: TDO2, TDO / Production host: Escherichia coli (E. coli) / References: UniProt: P48775, tryptophan 2,3-dioxygenase
#2: Chemical	ChemComp-HEM / PROTOPORPHYRIN IX CONTAINING FE / HEME Mass: 616.487 Da / Num. of mol.: 4 / Source method: obtained synthetically / Formula: C₃₄H₃₂FeN₄O₄ / Feature type: SUBJECT OF INVESTIGATION
#3: Chemical	ChemComp-ZIQ / alpha-methyl-L-tryptophan Type: L-peptide linking / Mass: 218.252 Da / Num. of mol.: 4 / Source method: obtained synthetically / Formula: C₁₂H₁₄N₂O₂ / Feature type: SUBJECT OF INVESTIGATION
#4: Chemical	ChemComp-A1AER / 6-fluoro-3-[(E)-2-(1H-tetrazol-5-yl)ethenyl]-1H-indole Mass: 229.213 Da / Num. of mol.: 3 / Source method: obtained synthetically / Formula: C₁₁H₈FN₅ / Feature type: SUBJECT OF INVESTIGATION
#5: Water	ChemComp-HOH / water Mass: 18.015 Da / Num. of mol.: 189 / Source method: isolated from a natural source / Formula: H₂O
Has ligand of interest	Y

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Experiment

Experiment	Method: X-RAY DIFFRACTION / Number of used crystals: 1

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Sample preparation

Crystal	Density Matthews: 2.66 Å³/Da / Density % sol: 53.75 %
Crystal grow	Temperature: 293 K / Method: batch mode Details: 50 mM sodium citrate, pH 5.6, 2% Tacsimate, pH 5.0, 5% PEG3350

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Data collection

Diffraction	Mean temperature: 100 K / Serial crystal experiment: N
Diffraction source	Source: SYNCHROTRON / Site: APS / Beamline: 31-ID / Wavelength: 0.97931 Å
Detector	Type: RAYONIX MX225HE / Detector: CCD / Date: Mar 1, 2017
Radiation	Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelength	Wavelength: 0.97931 Å / Relative weight: 1
Reflection	Resolution: 2.29→52.31 Å / Num. obs: 85859 / % possible obs: 97.258 % / Redundancy: 6.6 % / R_pim(I) all: 0.076 / Net I/σ(I): 6.6
Reflection shell	Resolution: 2.29→2.41 Å / R_merge(I) obs: 1.512 / Num. unique obs: 84922 / CC_1/2: 0.139

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Processing

Software

Name	Version	Classification
REFMAC	5.8.0267	refinement
MOSFLM		data reduction
SCALA		data scaling
PHASER		phasing

Refinement

Method to determine structure:

MOLECULAR REPLACEMENT / Resolution: 2.29→30.002 Å / Cor.coef. F_o:F_c: 0.956 / Cor.coef. F_o:F_c free: 0.942 / WR_factor R_free: 0.23 / WR_factor R_work: 0.192 / SU B: 10.066 / SU ML: 0.214 / Average fsc free: 0.8276 / Average fsc work: 0.8375 / Cross valid method: FREE R-VALUE / ESU R: 0.287 / ESU R Free: 0.216
Details: Hydrogens have been added in their riding positions

	R_factor	Num. reflection	% reflection
R_free	0.2381	4274	5.033 %
R_work	0.2023	80648	-
all	0.204	-	-
obs	-	84922	97.258 %

Solvent computation

Ion probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å / Solvent model: MASK BULK SOLVENT

Displacement parameters

B_iso mean: 57.005 Å²

	B_aniso -1	B_aniso -2	B_aniso -3
1-	-0.428 Å²	-0 Å²	-0 Å²
2-	-	-0.136 Å²	0 Å²
3-	-	-	0.564 Å²

Refinement step

Cycle: LAST / Resolution: 2.29→30.002 Å

	Protein	Nucleic acid	Ligand	Solvent	Total
Num. atoms	11483	0	287	189	11959

Refine LS restraints

Refine-ID	Type	Dev ideal	Dev ideal target	Number
X-RAY DIFFRACTION	r_bond_refined_d	0.009	0.013	12074
X-RAY DIFFRACTION	r_bond_other_d	0.001	0.015	11403
X-RAY DIFFRACTION	r_angle_refined_deg	1.76	1.681	16314
X-RAY DIFFRACTION	r_angle_other_deg	1.298	1.599	26145
X-RAY DIFFRACTION	r_dihedral_angle_1_deg	5.803	5	1344
X-RAY DIFFRACTION	r_dihedral_angle_2_deg	33.366	21.86	726
X-RAY DIFFRACTION	r_dihedral_angle_3_deg	18.416	15	2224
X-RAY DIFFRACTION	r_dihedral_angle_4_deg	16.728	15	93
X-RAY DIFFRACTION	r_chiral_restr	0.075	0.2	1413
X-RAY DIFFRACTION	r_gen_planes_refined	0.007	0.02	13431
X-RAY DIFFRACTION	r_gen_planes_other	0.003	0.02	3044
X-RAY DIFFRACTION	r_nbd_refined	0.223	0.2	2600
X-RAY DIFFRACTION	r_symmetry_nbd_other	0.179	0.2	10425
X-RAY DIFFRACTION	r_nbtor_refined	0.172	0.2	5723
X-RAY DIFFRACTION	r_symmetry_nbtor_other	0.078	0.2	5588
X-RAY DIFFRACTION	r_xyhbond_nbd_refined	0.167	0.2	279
X-RAY DIFFRACTION	r_symmetry_xyhbond_nbd_other	0.123	0.2	1
X-RAY DIFFRACTION	r_symmetry_nbd_refined	0.249	0.2	17
X-RAY DIFFRACTION	r_nbd_other	0.295	0.2	50
X-RAY DIFFRACTION	r_symmetry_xyhbond_nbd_refined	0.2	0.2	8
X-RAY DIFFRACTION	r_mcbond_it	5.659	5.796	5427
X-RAY DIFFRACTION	r_mcbond_other	5.656	5.795	5423
X-RAY DIFFRACTION	r_mcangle_it	8.457	8.668	6754
X-RAY DIFFRACTION	r_mcangle_other	8.459	8.67	6753
X-RAY DIFFRACTION	r_scbond_it	5.772	6.26	6647
X-RAY DIFFRACTION	r_scbond_other	5.771	6.26	6646
X-RAY DIFFRACTION	r_scangle_it	8.747	9.171	9560
X-RAY DIFFRACTION	r_scangle_other	8.747	9.172	9561
X-RAY DIFFRACTION	r_lrange_it	11.514	64.325	13920
X-RAY DIFFRACTION	r_lrange_other	11.52	64.337	13894
X-RAY DIFFRACTION	r_ncsr_local_group_1	0.088	0.05	11156
X-RAY DIFFRACTION	r_ncsr_local_group_2	0.09	0.05	10594
X-RAY DIFFRACTION	r_ncsr_local_group_3	0.093	0.05	11092
X-RAY DIFFRACTION	r_ncsr_local_group_4	0.096	0.05	10553
X-RAY DIFFRACTION	r_ncsr_local_group_5	0.09	0.05	11107
X-RAY DIFFRACTION	r_ncsr_local_group_6	0.094	0.05	10595

Refine LS restraints NCS

Ens-ID	Dom-ID	Auth asym-ID	Refine-ID	Type	Rms dev position (Å)	Weight position
1	1	AAA	X-RAY DIFFRACTION	Local ncs	0.08807	0.05008
1	2	BBB	X-RAY DIFFRACTION	Local ncs	0.08807	0.05008
2	3	AAA	X-RAY DIFFRACTION	Local ncs	0.08984	0.05008
2	4	CCC	X-RAY DIFFRACTION	Local ncs	0.08984	0.05008
3	5	AAA	X-RAY DIFFRACTION	Local ncs	0.09345	0.05008
3	6	DDD	X-RAY DIFFRACTION	Local ncs	0.09345	0.05008
4	7	BBB	X-RAY DIFFRACTION	Local ncs	0.09595	0.05008
4	8	CCC	X-RAY DIFFRACTION	Local ncs	0.09595	0.05008
5	9	BBB	X-RAY DIFFRACTION	Local ncs	0.0895	0.05008
5	10	DDD	X-RAY DIFFRACTION	Local ncs	0.0895	0.05008
6	11	CCC	X-RAY DIFFRACTION	Local ncs	0.09401	0.05008
6	12	DDD	X-RAY DIFFRACTION	Local ncs	0.09401	0.05008

LS refinement shell

Refine-ID: X-RAY DIFFRACTION / Total num. of bins used: 20

Resolution (Å)	R_factor R_free	Num. reflection R_free	R_factor R_work	Num. reflection R_work	R_factor all	Num. reflection all	Fsc free	Fsc work	% reflection obs (%)	WR_factor R_work
2.29-2.349	0.364	265	0.369	4948	0.369	6353	0.498	0.523	82.0557	0.368
2.349-2.413	0.362	284	0.363	5441	0.363	6168	0.57	0.561	92.8178	0.361
2.413-2.483	0.352	297	0.345	5515	0.345	6015	0.652	0.658	96.6251	0.344
2.483-2.558	0.338	265	0.319	5462	0.32	5883	0.725	0.727	97.3483	0.316
2.558-2.642	0.354	268	0.294	5261	0.297	5664	0.784	0.801	97.6165	0.287
2.642-2.734	0.307	272	0.279	5159	0.281	5521	0.816	0.826	98.3699	0.266
2.734-2.836	0.298	264	0.242	4982	0.245	5303	0.863	0.881	98.9251	0.227
2.836-2.951	0.281	260	0.225	4816	0.227	5119	0.881	0.902	99.16	0.206
2.951-3.081	0.272	269	0.21	4595	0.213	4899	0.896	0.913	99.2856	0.192
3.081-3.229	0.252	239	0.205	4479	0.207	4732	0.912	0.924	99.7041	0.19
3.229-3.402	0.244	231	0.192	4252	0.194	4495	0.919	0.94	99.733	0.178
3.402-3.605	0.239	226	0.194	4035	0.196	4269	0.93	0.941	99.8126	0.184
3.605-3.85	0.215	202	0.178	3817	0.18	4020	0.945	0.958	99.9751	0.173
3.85-4.153	0.176	181	0.142	3586	0.143	3767	0.966	0.973	100	0.141
4.153-4.54	0.162	181	0.136	3294	0.137	3475	0.97	0.971	100	0.141
4.54-5.062	0.176	153	0.141	3001	0.142	3154	0.964	0.971	100	0.148
5.062-5.818	0.193	125	0.164	2714	0.165	2839	0.962	0.969	100	0.17
5.818-7.059	0.224	124	0.187	2285	0.189	2409	0.946	0.959	100	0.195
7.059-9.717	0.196	108	0.156	1841	0.158	1950	0.962	0.97	99.9487	0.181
9.717-30.002	0.25	60	0.23	1165	0.231	1228	0.946	0.954	99.7557	0.267

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