PDB-8tft: Fab of O13-1 human IgG1 antibody bound to IgV domain of human TIM-3

ID or keywords:

Entry

Database: PDB / ID: 8tft

Title

Fab of O13-1 human IgG1 antibody bound to IgV domain of human TIM-3

Components

O-13-1 IgG1 Fab heavy chain
O-13-1 IgG1 Fab light chain
T-cell immunoglobulin mucin receptor 3

Keywords

IMMUNE SYSTEM / Fragment antigen binding / antibody / T-cell immunoglobulin mucin receptor 3 (TIM-3) / IgV type domain

Function / homology

Function and homology information

regulation of tolerance induction dependent upon immune response / negative regulation of interleukin-3 production / negative regulation of granulocyte colony-stimulating factor production / negative regulation of myeloid dendritic cell activation / Interleukin-2 family signaling / negative regulation of interferon-alpha production / negative regulation of T-helper 1 type immune response / negative regulation of defense response to bacterium / toll-like receptor 7 signaling pathway / natural killer cell tolerance induction ...regulation of tolerance induction dependent upon immune response / negative regulation of interleukin-3 production / negative regulation of granulocyte colony-stimulating factor production / negative regulation of myeloid dendritic cell activation / Interleukin-2 family signaling / negative regulation of interferon-alpha production / negative regulation of T-helper 1 type immune response / negative regulation of defense response to bacterium / toll-like receptor 7 signaling pathway / natural killer cell tolerance induction / negative regulation of natural killer cell activation / negative regulation of natural killer cell mediated cytotoxicity directed against tumor cell target / positive regulation of defense response to bacterium / negative regulation of immunological synapse formation / toll-like receptor 3 signaling pathway / negative regulation of T cell activation via T cell receptor contact with antigen bound to MHC molecule on antigen presenting cell / positive regulation of interleukin-1 production / toll-like receptor 9 signaling pathway / mediator complex / macrophage activation involved in immune response / positive regulation of macrophage activation / anchoring junction / negative regulation of interleukin-2 production / negative regulation of NF-kappaB transcription factor activity / positive regulation of interleukin-4 production / negative regulation of interleukin-6 production / negative regulation of type II interferon production / negative regulation of tumor necrosis factor production / immunological synapse / maternal process involved in female pregnancy / positive regulation of T cell proliferation / positive regulation of chemokine production / negative regulation of T cell proliferation / positive regulation of non-canonical NF-kappaB signal transduction / positive regulation of type II interferon production / positive regulation of tumor necrosis factor production / transmembrane signaling receptor activity / cellular response to lipopolysaccharide / adaptive immune response / early endosome / positive regulation of ERK1 and ERK2 cascade / defense response to Gram-positive bacterium / inflammatory response / innate immune response / negative regulation of gene expression / regulation of transcription by RNA polymerase II / cell surface / metal ion binding / plasma membrane
Similarity search - Function

Biological species

Homo sapiens (human)

Method

X-RAY DIFFRACTION /

SYNCHROTRON /

MOLECULAR REPLACEMENT / Resolution: 2.3 Å

Authors

Oganesyan, V.Y. / van Dyk, N. / Mazor, Y. / Yang, C.

Funding support

1items

Citation

Journal: To be published
Title: Generation of AZD7789, a novel PD-1 and TIM-3 targeting bispecific antibody, which binds to a differentiated epitope of TIM-3
Authors: Clancy-Thompson, E. / Perry, T. / Pryts, S. / Jaiswal, A. / Oganesyan, V. / Moynihan, J. / van Dyk, N. / Yang, C. / Garcia, A. / Yu, J. / Miller, C. / Mulgrew, K. / Cobbold, M. / Mazor, Y. / ...

History

Deposition	Jul 11, 2023	Deposition site: RCSB / Processing site: RCSB
Revision 1.0	Aug 28, 2024	Provider: repository / Type: Initial release
Revision 1.1	Oct 30, 2024	Group: Structure summary / Category: pdbx_entry_details / pdbx_modification_feature / Item: _pdbx_entry_details.has_protein_modification

Structure viewer	Molecule: MolmilJmol/JSmol

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Download

PDBx/mmCIF format	8tft.cif.gz	223.8 KB	Display	PDBx/mmCIF format
PDB format	pdb8tft.ent.gz	172.6 KB	Display	PDB format
PDBx/mmJSON format	8tft.json.gz		Tree view	PDBx/mmJSON format
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Validation report

Summary document	8tft_validation.pdf.gz	498.5 KB	Display	wwPDB validaton report
Full document	8tft_full_validation.pdf.gz	511.4 KB	Display
Data in XML	8tft_validation.xml.gz	38.1 KB	Display
Data in CIF	8tft_validation.cif.gz	52.1 KB	Display
Arichive directory	https://data.pdbj.org/pub/pdb/validation_reports/tf/8tft ftp://data.pdbj.org/pub/pdb/validation_reports/tf/8tft	HTTPS FTP

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Related structure data

Related structure data	8tbbC 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
Related items in Molecule of the Month	#21 - Sep 2001 Antibodies similarity (1) #256 - Apr 2021 SARS-CoV-2 Spike and Antibodies similarity (1)

Deposited unit

I: O-13-1 IgG1 Fab heavy chain

M: O-13-1 IgG1 Fab light chain

F: T-cell immunoglobulin mucin receptor 3

H: O-13-1 IgG1 Fab heavy chain

L: O-13-1 IgG1 Fab light chain

G: T-cell immunoglobulin mucin receptor 3

hetero molecules

119 kDa, 6 polymers
Search similar-shape structures of this assembly by Omokage search (details)

1

I: O-13-1 IgG1 Fab heavy chain

M: O-13-1 IgG1 Fab light chain

F: T-cell immunoglobulin mucin receptor 3

hetero molecules

defined by author
59.4 kDa, 3 polymers
Search similar-shape structures of this assembly by Omokage search (details)

2

H: O-13-1 IgG1 Fab heavy chain

L: O-13-1 IgG1 Fab light chain

G: T-cell immunoglobulin mucin receptor 3

hetero molecules

defined by author
59.4 kDa, 3 polymers
Search similar-shape structures of this assembly by Omokage search (details)

Unit cell

Length a, b, c (Å)	218.338, 69.785, 93.632
Angle α, β, γ (deg.)	90.000, 99.897, 90.000
Int Tables number	5
Space group name H-M	C121

Noncrystallographic symmetry (NCS)

NCS domain:

ID	Ens-ID	Details
1	1	I
2	1	I
3	2	I
4	2	I
5	3	I
6	3	I

NCS domain segments:

Beg auth comp-ID: GLU / Beg label comp-ID: GLU / Auth asym-ID: I / Label asym-ID: A

Dom-ID	Component-ID	Ens-ID	End auth comp-ID	End label comp-ID	Auth seq-ID	Label seq-ID
1	1	1	SER	SER	1 - 224	1 - 224
2	1	1	SER	SER	1 - 224	1 - 224
3	2	2	LYS	LYS	1 - 210	1 - 210
4	2	2	LYS	LYS	1 - 210	1 - 210
5	3	3	PHE	PHE	1 - 109	1 - 109
6	3	3	PHE	PHE	1 - 109	1 - 109

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

#1: Antibody

O-13-1 IgG1 Fab heavy chain

Mass: 24018.725 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
Source: (gene. exp.)

Homo sapiens (human) / Production host:

Cricetulus griseus (Chinese hamster)

#2: Antibody

O-13-1 IgG1 Fab light chain

Mass: 22846.352 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
Source: (gene. exp.)

Homo sapiens (human) / Production host:

Cricetulus griseus (Chinese hamster)

#3: Protein

T-cell immunoglobulin mucin receptor 3 / Hepatitis A virus cellular receptor 2 / HAVcr-2 / T-cell immunoglobulin and mucin domain-containing ...

Mass: 12298.002 Da / Num. of mol.: 2 / Fragment: IgV domain
Source method: isolated from a genetically manipulated source
Source: (gene. exp.)

Homo sapiens (human) / Gene: HAVCR2, TIM3, TIMD3 / Production host:

Homo sapiens (human) / References: UniProt: Q8TDQ0

#4: Sugar

ChemComp-NAG / 2-acetamido-2-deoxy-beta-D-glucopyranose / N-acetyl-beta-D-glucosamine / 2-acetamido-2-deoxy-beta-D-glucose / 2-acetamido-2-deoxy-D-glucose / 2-acetamido-2-deoxy-glucose / N-ACETYL-D-GLUCOSAMINE

Type: D-saccharide, beta linking / Mass: 221.208 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
Formula: C₈H₁₅NO₆

Identifier	Type	Program
DGlcpNAcb	CONDENSED IUPAC CARBOHYDRATE SYMBOL	GMML 1.0
N-acetyl-b-D-glucopyranosamine	COMMON NAME	GMML 1.0
b-D-GlcpNAc	IUPAC CARBOHYDRATE SYMBOL	PDB-CARE 1.0
GlcNAc	SNFG CARBOHYDRATE SYMBOL	GMML 1.0

#5: Water

ChemComp-HOH / water

Mass: 18.015 Da / Num. of mol.: 27 / Source method: isolated from a natural source / Formula: H₂O

Has ligand of interest

N

Has protein modification

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: 2.98 Å³/Da / Density % sol: 58.66 %
Crystal grow	Temperature: 293 K / Method: vapor diffusion Details: 0.1 MIB buffer (Sodium malonate dibasic monohydrate, Imidazole, Boric acid), pH 6.0 and 25% w/v PEG 1500

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Data collection

Diffraction	Mean temperature: 100 K / Serial crystal experiment: N
Diffraction source	Source: SYNCHROTRON / Site: SSRL / Beamline: BL14-1 / Wavelength: 0.97 Å
Detector	Type: DECTRIS PILATUS 6M / Detector: PIXEL / Date: Jan 14, 2017
Radiation	Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelength	Wavelength: 0.97 Å / Relative weight: 1
Reflection	Resolution: 2.2→38.9 Å / Num. obs: 69615 / % possible obs: 98.3 % / Redundancy: 3.5 % / CC_1/2: 0.93 / R_merge(I) obs: 0.065 / Net I/σ(I): 9.1
Reflection shell	Resolution: 2.2→2.5 Å / Num. unique obs: 436 / CC_1/2: 0.66

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Processing

Software

Name	Version	Classification
REFMAC	5.8.0415	refinement
XDS		data reduction
XDS		data scaling
MOLREP		phasing

Refinement

Method to determine structure:

MOLECULAR REPLACEMENT / Resolution: 2.3→37.003 Å / Cor.coef. F_o:F_c: 0.946 / Cor.coef. F_o:F_c free: 0.93 / SU B: 11.076 / SU ML: 0.244 / Cross valid method: THROUGHOUT / ESU R: 0.319 / ESU R Free: 0.236
Details: Hydrogens have been added in their riding positions

	R_factor	Num. reflection	% reflection
R_free	0.2711	1218	1.999 %
R_work	0.2443	59710	-
all	0.245	-	-
obs	-	60928	98.228 %

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: 60.959 Å²

	B_aniso -1	B_aniso -2	B_aniso -3
1-	-0.673 Å²	0 Å²	-4.112 Å²
2-	-	0.539 Å²	0 Å²
3-	-	-	1.479 Å²

Refinement step

Cycle: LAST / Resolution: 2.3→37.003 Å

	Protein	Nucleic acid	Ligand	Solvent	Total
Num. atoms	8259	0	28	27	8314

Refine LS restraints

Refine-ID	Type	Dev ideal	Dev ideal target	Number
X-RAY DIFFRACTION	r_bond_refined_d	0.003	0.011	8493
X-RAY DIFFRACTION	r_bond_other_d	0.001	0.016	7730
X-RAY DIFFRACTION	r_angle_refined_deg	0.964	1.661	11578
X-RAY DIFFRACTION	r_angle_other_deg	0.335	1.571	17883
X-RAY DIFFRACTION	r_dihedral_angle_1_deg	7.25	5	1084
X-RAY DIFFRACTION	r_dihedral_angle_2_deg	5.876	5	40
X-RAY DIFFRACTION	r_dihedral_angle_3_deg	14.095	10	1293
X-RAY DIFFRACTION	r_dihedral_angle_6_deg	14.052	10	333
X-RAY DIFFRACTION	r_chiral_restr	0.042	0.2	1286
X-RAY DIFFRACTION	r_gen_planes_refined	0.004	0.02	10060
X-RAY DIFFRACTION	r_gen_planes_other	0.001	0.02	1924
X-RAY DIFFRACTION	r_nbd_refined	0.206	0.2	1350
X-RAY DIFFRACTION	r_symmetry_nbd_other	0.192	0.2	6958
X-RAY DIFFRACTION	r_nbtor_refined	0.176	0.2	4027
X-RAY DIFFRACTION	r_symmetry_nbtor_other	0.082	0.2	4563
X-RAY DIFFRACTION	r_xyhbond_nbd_refined	0.309	0.2	208
X-RAY DIFFRACTION	r_symmetry_xyhbond_nbd_other	0.014	0.2	1
X-RAY DIFFRACTION	r_symmetry_nbd_refined	0.181	0.2	26
X-RAY DIFFRACTION	r_nbd_other	0.148	0.2	104
X-RAY DIFFRACTION	r_symmetry_xyhbond_nbd_refined	0.374	0.2	10
X-RAY DIFFRACTION	r_xyhbond_nbd_other	0.001	0.2	2
X-RAY DIFFRACTION	r_mcbond_it	3.573	6.099	4354
X-RAY DIFFRACTION	r_mcbond_other	3.573	6.099	4354
X-RAY DIFFRACTION	r_mcangle_it	5.829	10.949	5432
X-RAY DIFFRACTION	r_mcangle_other	5.828	10.95	5433
X-RAY DIFFRACTION	r_scbond_it	3.049	6.222	4139
X-RAY DIFFRACTION	r_scbond_other	3.049	6.223	4140
X-RAY DIFFRACTION	r_scangle_it	5.119	11.353	6146
X-RAY DIFFRACTION	r_scangle_other	5.119	11.353	6147
X-RAY DIFFRACTION	r_lrange_it	8.443	56.02	8783
X-RAY DIFFRACTION	r_lrange_other	8.443	56.034	8780
X-RAY DIFFRACTION	r_ncsr_local_group_1	0.093	0.05	6511
X-RAY DIFFRACTION	r_ncsr_local_group_2	0.096	0.05	6098
X-RAY DIFFRACTION	r_ncsr_local_group_3	0.117	0.05	3242

Refine LS restraints NCS

Ens-ID	Dom-ID	Auth asym-ID	Refine-ID	Type	Rms dev position (Å)	Weight position
1	1	I	X-RAY DIFFRACTION	Local ncs	0.09301	0.0501
1	2	I	X-RAY DIFFRACTION	Local ncs	0.09301	0.0501
2	3	I	X-RAY DIFFRACTION	Local ncs	0.09636	0.0501
2	4	I	X-RAY DIFFRACTION	Local ncs	0.09636	0.0501
3	5	I	X-RAY DIFFRACTION	Local ncs	0.11743	0.0501
3	6	I	X-RAY DIFFRACTION	Local ncs	0.11743	0.0501

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
2.3-2.359	0.427	80	0.388	4279	0.389	4534	0.854	0.887	96.1403	0.388
2.359-2.424	0.381	93	0.377	4272	0.377	4432	0.91	0.897	98.4883	0.377
2.424-2.494	0.38	98	0.36	4174	0.36	4315	0.896	0.91	99.0035	0.36
2.494-2.57	0.336	67	0.351	4070	0.351	4188	0.906	0.916	98.7822	0.351
2.57-2.654	0.309	70	0.338	3934	0.337	4069	0.933	0.928	98.4026	0.338
2.654-2.747	0.356	82	0.314	3731	0.315	3904	0.915	0.934	97.6691	0.314
2.747-2.85	0.333	82	0.301	3582	0.302	3801	0.939	0.944	96.3957	0.301
2.85-2.965	0.248	73	0.274	3512	0.273	3624	0.948	0.955	98.9238	0.274
2.965-3.096	0.332	67	0.269	3417	0.27	3507	0.929	0.956	99.3442	0.269
3.096-3.246	0.281	80	0.28	3259	0.28	3358	0.949	0.951	99.4342	0.28
3.246-3.421	0.263	64	0.277	3090	0.277	3192	0.958	0.955	98.8095	0.277
3.421-3.626	0.337	53	0.284	2912	0.285	3025	0.94	0.956	98.0165	0.284
3.626-3.874	0.29	56	0.271	2748	0.271	2875	0.948	0.959	97.5304	0.271
3.874-4.18	0.246	44	0.221	2581	0.221	2642	0.965	0.974	99.3566	0.221
4.18-4.574	0.243	47	0.184	2384	0.185	2460	0.957	0.981	98.8211	0.184
4.574-5.104	0.162	43	0.164	2145	0.164	2223	0.986	0.985	98.4256	0.164
5.104-5.875	0.215	41	0.185	1898	0.185	1998	0.981	0.983	97.0471	0.185
5.875-7.15	0.265	38	0.19	1631	0.192	1684	0.967	0.981	99.1093	0.19
7.15-9.928	0.221	29	0.166	1284	0.168	1339	0.981	0.985	98.0583	0.166
9.928-37.003	0.269	10	0.212	783	0.212	813	0.953	0.967	97.54	0.212

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