PDB-8g2m: The tumor activated anti-CTLA-4 monoclonal antibody XTX101 demons...

ID or keywords:

Entry

Database: PDB / ID: 8g2m

Title

The tumor activated anti-CTLA-4 monoclonal antibody XTX101 demonstrates tumor-growth inhibition and tumor-selective pharmacodynamics in mouse models of cancer

Components

Heavy chain of humanized IgG
Light chain of humanized IgG
masking peptide

Keywords

IMMUNE SYSTEM / Engineered antibody

Function / homology

CITRIC ACID

Function and homology information

Biological species

Mus musculus (house mouse)
Peptide display vector fth1 (others)

Method

X-RAY DIFFRACTION /

MOLECULAR REPLACEMENT / Resolution: 1.8 Å

Authors

Williams, J.C. / Williams, J.C.

Funding support

1items

Citation

Journal: J Immunother Cancer / Year: 2023
Title: XTX101, a tumor-activated, Fc-enhanced anti-CTLA-4 monoclonal antibody, demonstrates tumor-growth inhibition and tumor-selective pharmacodynamics in mouse models of cancer.
Authors: Jenkins, K.A. / Park, M. / Pederzoli-Ribeil, M. / Eskiocak, U. / Johnson, P. / Guzman, W. / McLaughlin, M. / Moore-Lai, D. / O'Toole, C. / Liu, Z. / Nicholson, B. / Flesch, V. / Qiu, H. / ...

History

Deposition	Feb 5, 2023	Deposition site: RCSB / Processing site: RCSB
Revision 1.0	Feb 14, 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	8g2m.cif.gz	197.2 KB	Display	PDBx/mmCIF format
PDB format	pdb8g2m.ent.gz	154.5 KB	Display	PDB format
PDBx/mmJSON format	8g2m.json.gz		Tree view	PDBx/mmJSON format
Others	Other downloads

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Validation report

Summary document	8g2m_validation.pdf.gz	453.9 KB	Display	wwPDB validaton report
Full document	8g2m_full_validation.pdf.gz	455.8 KB	Display
Data in XML	8g2m_validation.xml.gz	23.1 KB	Display
Data in CIF	8g2m_validation.cif.gz	35.8 KB	Display
Arichive directory	https://data.pdbj.org/pub/pdb/validation_reports/g2/8g2m ftp://data.pdbj.org/pub/pdb/validation_reports/g2/8g2m	HTTPS FTP

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Related structure data

Related structure data	8g8nC C: citing same article (ref.)
Similar structure data	Similarity search - Function & homologyF&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

F: masking peptide

H: Heavy chain of humanized IgG

L: Light chain of humanized IgG

hetero molecules

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

1

Idetical with deposited unit
defined by author&software
Evidence: surface plasmon resonance

Unit cell

Length a, b, c (Å)	130.180, 55.230, 73.860
Angle α, β, γ (deg.)	90.00, 118.70, 90.00
Int Tables number	5
Space group name H-M	C121

Components on special symmetry positions

ID	Model	Components
1	1	L-591- HOH

#1: Protein/peptide	masking peptide Mass: 992.211 Da / Num. of mol.: 1 / Source method: obtained synthetically / Source: (synth.) Peptide display vector fth1 (others)
#2: Antibody	Heavy chain of humanized IgG Mass: 23624.594 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Mus musculus (house mouse) / Production host: Cricetulus griseus (Chinese hamster)
#3: Protein	Light chain of humanized IgG Mass: 22294.537 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Mus musculus (house mouse) / Production host: Cricetulus griseus (Chinese hamster)
#4: Chemical	ChemComp-CIT / CITRIC ACID Mass: 192.124 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C₆H₈O₇
#5: Water	ChemComp-HOH / water Mass: 18.015 Da / Num. of mol.: 541 / 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: 2.48 Å³/Da / Density % sol: 50.45 %
Crystal grow	Temperature: 298 K / Method: vapor diffusion, hanging drop Details: 0.2 M Ammonium Citrate Dibasic pH 5.0, 20% PEG 3350

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Data collection

Diffraction	Mean temperature: 100 K / Serial crystal experiment: N
Diffraction source	Source: ROTATING ANODE / Type: RIGAKU MICROMAX-007 HF / Wavelength: 1.5418 Å
Detector	Type: RIGAKU HyPix-6000HE / Detector: PIXEL / Date: Jan 3, 2023
Radiation	Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelength	Wavelength: 1.5418 Å / Relative weight: 1
Reflection	Resolution: 1.8→28.98 Å / Num. obs: 42381 / % possible obs: 96.99 % / Redundancy: 8.3 % / CC_1/2: 0.999 / R_merge(I) obs: 0.0645 / R_pim(I) all: 0.0228 / R_rim(I) all: 0.06861 / Net I/σ(I): 21.67
Reflection shell	Resolution: 1.8→1.864 Å / R_merge(I) obs: 0.5691 / Mean I/σ(I) obs: 2.05 / Num. unique obs: 3390 / CC_1/2: 0.848 / R_pim(I) all: 0.3137

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Processing

Software

Name	Version	Classification
PHENIX	v1	refinement
XDS		data reduction
XDS		data scaling
PHASER		phasing

Refinement

Method to determine structure:

MOLECULAR REPLACEMENT / Resolution: 1.8→28.98 Å / Cor.coef. F_o:F_c: 0.96 / Cor.coef. F_o:F_c free: 0.946 / SU B: 5.741 / SU ML: 0.094 / Cross valid method: THROUGHOUT / ESU R: 0.135 / ESU R Free: 0.124 / Stereochemistry target values: MAXIMUM LIKELIHOOD
Details: U VALUES : WITH TLS ADDED HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS U VALUES : RESIDUAL ONLY

	R_factor	Num. reflection	% reflection	Selection details
R_free	0.21395	2120	5.1 %	RANDOM
R_work	0.1798	-	-	-
obs	0.18155	39463	97.02 %	-

Solvent computation

Ion probe radii: 0.7 Å / Shrinkage radii: 0.7 Å / VDW probe radii: 1 Å / Solvent model: MASK

Displacement parameters

B_iso mean: 26.199 Å²

	B_aniso -1	B_aniso -2	B_aniso -3
1-	0.01 Å²	0 Å²	-0.3 Å²
2-	-	-0.18 Å²	-0 Å²
3-	-	-	0.31 Å²

Refinement step

Cycle: LAST / Resolution: 1.8→28.98 Å

	Protein	Nucleic acid	Ligand	Solvent	Total
Num. atoms	3298	0	13	541	3852

Refine LS restraints

Refine-ID	Type	Dev ideal	Dev ideal target	Number
X-RAY DIFFRACTION	r_bond_refined_d	0.01	0.016	3456
X-RAY DIFFRACTION	r_bond_other_d	0.001	0.016	3027
X-RAY DIFFRACTION	r_angle_refined_deg	1.282	1.81	4718
X-RAY DIFFRACTION	r_angle_other_deg	0.444	1.563	7114
X-RAY DIFFRACTION	r_dihedral_angle_1_deg	7.119	5.12	458
X-RAY DIFFRACTION	r_dihedral_angle_3_deg	12.503	10	550
X-RAY DIFFRACTION	r_chiral_restr	0.067	0.2	521
X-RAY DIFFRACTION	r_gen_planes_refined	0.006	0.02	3926
X-RAY DIFFRACTION	r_gen_planes_other	0.001	0.02	678
X-RAY DIFFRACTION	r_mcbond_it	1.832	0.926	1756
X-RAY DIFFRACTION	r_mcbond_other	1.827	0.926	1756
X-RAY DIFFRACTION	r_mcangle_it	2.471	1.371	2197
X-RAY DIFFRACTION	r_mcangle_other	2.471	1.372	2198
X-RAY DIFFRACTION	r_scbond_it	3.559	1.175	1700
X-RAY DIFFRACTION	r_scbond_other	3.409	1.165	1697
X-RAY DIFFRACTION	r_scangle_other	4.805	1.643	2516
X-RAY DIFFRACTION	r_long_range_B_refined	7.287	17.53	3805
X-RAY DIFFRACTION	r_long_range_B_other	7.162	14.102	3625

LS refinement shell

Resolution: 1.8→1.847 Å / Total num. of bins used: 20

	R_factor	Num. reflection	% reflection
R_free	0.293	108	-
R_work	0.259	2320	-
obs	-	-	76.79 %

Refinement TLS params.

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

ID	L11 (°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)
1	6.193	-1.3462	-7.7028	0.7849	-0.2358	17.0596	-0.0178	-0.0747	0.635	0.3247	0.2745	-0.2453	-1.1507	-0.8038	-0.2567	0.2877	0.1177	-0.0183	0.2119	0.0079	0.2423	-34.592	32.901	8.323
2	5.0702	-0.5144	2.6255	4.087	-0.5223	2.8404	0.0031	1.0271	-0.2404	0.2681	-0.0492	-0.7928	-0.1485	0.7913	0.0461	0.0399	-0.0187	-0.0975	0.2561	-0.0411	0.2911	-8.482	27.178	10.776
3	4.3389	-0.4152	3.883	1.5624	0.4748	3.9557	0.0699	0.2198	0.0938	-0.1459	-0.0471	-0.2483	-0.0415	0.2103	-0.0227	0.0733	-0.0394	-0.0217	0.1285	0.068	0.0806	-17.641	31.724	2.571
4	3.2674	0.302	0.3582	3.8217	0.6123	4.0596	0.0079	-0.1458	0.1938	0.3531	0.0007	-0.0649	-0.3457	-0.0875	-0.0086	0.1105	0.0108	-0.0444	0.0196	-0.0087	0.0547	-20.957	31.473	14.256
5	3.1925	-2.2148	2.3689	2.9049	-0.6882	5.8877	-0.1847	-0.3422	0.2916	0.4327	0.3072	-0.1292	-0.2588	-0.5614	-0.1226	0.2233	0.0252	-0.0762	0.0916	0.0528	0.1856	-11.724	31.268	17.79
6	3.419	-1.7452	0.7274	2.2918	-1.2606	0.8621	-0.1386	0.3317	0.4739	0.1268	-0.123	-0.4057	-0.1317	0.1206	0.2615	0.0529	-0.0415	-0.0531	0.0772	0.067	0.1038	-10.92	19.916	13.412
7	4.1904	-2.3431	2.0659	13.1353	0.5588	3.5094	-0.0246	0.1547	-0.3616	0.4578	0.0438	-0.3232	0.4449	0.1343	-0.0192	0.0864	0.0232	0.0263	0.1844	0.0288	0.1131	7.163	-4.03	24.196
8	2.4419	-1.0168	0.7651	6.8219	0.9472	1.4153	-0.1022	0.3583	0.2333	-0.292	-0.0447	-0.5333	-0.0081	0.3486	0.1469	0.0998	-0.0107	0.0061	0.2509	0.0632	0.1029	7.091	3.207	17.868
9	6.3373	-4.505	-2.0861	9.5229	2.0446	2.4753	0.0907	-0.3075	0.0487	0.2705	-0.0328	-0.4663	0.1528	-0.0516	-0.058	0.1205	-0.0139	-0.0273	0.0706	0.0326	0.044	-28.195	0.821	17.496
10	2.7954	0.5143	2.7277	5.8748	0.1532	4.5185	-0.0499	0.1501	-0.0356	0.126	-0.0166	0.1182	-0.1562	-0.1409	0.0665	0.0171	0.0076	-0.011	0.0567	-0.0151	0.0193	-26.337	13.896	10.534
11	2.0796	-1.6484	-0.1459	6.1341	2.8482	5.5541	0.0368	0.137	-0.1133	-0.0469	-0.1912	0.1433	-0.1128	-0.2847	0.1544	0.0161	0.006	-0.0116	0.077	-0.0133	0.0134	-34.386	8.787	9.35
12	2.1441	-1.8837	0.1692	10.6739	-0.6629	1.5064	-0.0424	0.0099	-0.1023	0.6165	-0.0081	0.1047	-0.0536	-0.121	0.0505	0.0477	-0.0174	-0.006	0.0978	0.0061	0.015	-26.353	10.644	15.148
13	5.7986	1.882	3.1323	2.4428	1.246	2.191	0.0045	0.1136	0.0845	-0.0491	-0.0539	-0.0533	-0.062	0.0857	0.0494	0.0527	0.0163	-0.0315	0.056	0.0064	0.0328	-0.928	-3.474	29.757
14	2.6927	0.9471	0.2939	0.4191	0.9468	8.4048	0.0852	0.0054	-0.1839	0.0467	-0.0269	-0.0663	0.2753	-0.5325	-0.0584	0.1735	0.007	-0.0536	0.1204	-0.0152	0.0893	-2.759	1.319	38.061
15	5.7878	1.0624	4.082	2.1975	0.9736	4.5177	0.0159	0.1503	0.0817	0.075	-0.0737	-0.0652	0.0018	0.2515	0.0579	0.0207	0.0178	-0.0007	0.0569	-0.0005	0.0329	0.219	-1.599	31.779
16	17.4937	2.6463	6.5128	3.1608	0.6399	3.8061	0.5587	0.0011	-0.8207	0.1283	-0.1442	-0.1921	0.4219	0.1129	-0.4144	0.1436	0.0116	-0.01	0.0721	-0.0151	0.1044	-0.968	-10.805	34.699

Refinement TLS group

ID	Refine-ID	Refine TLS-ID	Selection details	Auth asym-ID	Auth seq-ID
1	X-RAY DIFFRACTION	1	( CHAIN F AND RESID 1:9 )	F	1 - 9
2	X-RAY DIFFRACTION	2	( CHAIN H AND RESID 1:17 )	H	1 - 17
3	X-RAY DIFFRACTION	3	( CHAIN H AND RESID 18:32 )	H	18 - 32
4	X-RAY DIFFRACTION	4	( CHAIN H AND RESID 33:76 )	H	33 - 76
5	X-RAY DIFFRACTION	5	( CHAIN H AND RESID 77:91 )	H	77 - 91
6	X-RAY DIFFRACTION	6	( CHAIN H AND RESID 92:130 )	H	92 - 130
7	X-RAY DIFFRACTION	7	( CHAIN H AND RESID 131:151 )	H	131 - 151
8	X-RAY DIFFRACTION	8	( CHAIN H AND RESID 152:221 )	H	152 - 221
9	X-RAY DIFFRACTION	9	( CHAIN L AND RESID 9:25 )	L	9 - 25
10	X-RAY DIFFRACTION	10	( CHAIN L AND RESID 26:48 )	L	26 - 48
11	X-RAY DIFFRACTION	11	( CHAIN L AND RESID 49:75 )	L	49 - 75
12	X-RAY DIFFRACTION	12	( CHAIN L AND RESID 76:107 )	L	76 - 107
13	X-RAY DIFFRACTION	13	( CHAIN L AND RESID 108:150 )	L	108 - 150
14	X-RAY DIFFRACTION	14	( CHAIN L AND RESID 151:163 )	L	151 - 163
15	X-RAY DIFFRACTION	15	( CHAIN L AND RESID 164:197 )	L	164 - 197
16	X-RAY DIFFRACTION	16	( CHAIN L AND RESID 198:213 )	L	198 - 213

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