PDB-7p0k: Crystal structure of Autotaxin (ENPP2) with 18F-labeled positron ...

ID or keywords:

Entry

Database: PDB / ID: 7p0k

Title

Crystal structure of Autotaxin (ENPP2) with 18F-labeled positron emission tomography ligand

Components

Isoform 2 of Ectonucleotide pyrophosphatase/phosphodiesterase family member 2

Keywords

HYDROLASE / Autotaxin (ATX) / lysophosphatidic acid (LPA) / fluorine-18 / positron emission tomography (PET) / inflammation

Function / homology

Function and homology information

response to polycyclic arene / alkylglycerophosphoethanolamine phosphodiesterase / sphingolipid catabolic process / phospholipid catabolic process / phosphatidylcholine catabolic process / positive regulation of lamellipodium morphogenesis / lysophospholipase activity / phosphodiesterase I activity / scavenger receptor activity / alkylglycerophosphoethanolamine phosphodiesterase activity ...
Similarity search - Function

Biological species

Rattus norvegicus (Norway rat)

Method

X-RAY DIFFRACTION /

SYNCHROTRON /

MOLECULAR REPLACEMENT / Resolution: 2.2 Å

Authors

Salgado-Polo, F. / Shao, T. / Xiao, Z. / Van, R. / Chen, J. / Rong, J. / Haider, A. / Shao, Y. / Josephson, L. / Perrakis, A. / Liang, S.H.

Funding support

Netherlands, 1items

Citation

Journal: J Med Chem / Year: 2021
Title: Imaging Autotaxin In Vivo with 18 F-Labeled Positron Emission Tomography Ligands
Authors: Deng, X. / Salgado-Polo, F. / Shao, T. / Xiao, Z. / Van, R. / Chen, J. / Rong, J. / Haider, A. / Shao, Y. / Josephson, L. / Perrakis, A. / Liang, S.H.

History

Deposition	Jun 29, 2021	Deposition site: PDBE / Processing site: PDBE
Revision 1.0	Jul 13, 2022	Provider: repository / Type: Initial release
Revision 1.1	Jan 31, 2024	Group: Data collection / Refinement description Category: chem_comp_atom / chem_comp_bond / pdbx_initial_refinement_model

Structure viewer	Molecule: MolmilJmol/JSmol

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Download

PDBx/mmCIF format	7p0k.cif.gz	571.2 KB	Display	PDBx/mmCIF format
PDB format	pdb7p0k.ent.gz		Display	PDB format
PDBx/mmJSON format	7p0k.json.gz		Tree view	PDBx/mmJSON format
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Validation report

Summary document	7p0k_validation.pdf.gz	1.2 MB	Display	wwPDB validaton report
Full document	7p0k_full_validation.pdf.gz	1.2 MB	Display
Data in XML	7p0k_validation.xml.gz	31.8 KB	Display
Data in CIF	7p0k_validation.cif.gz	46.3 KB	Display
Arichive directory	https://data.pdbj.org/pub/pdb/validation_reports/p0/7p0k ftp://data.pdbj.org/pub/pdb/validation_reports/p0/7p0k	HTTPS FTP

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Related structure data

Related structure data	2xr9S S: Starting model for refinement
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	#50 - Feb 2004 Glycolytic Enzymes similarity (1) #190 - Oct 2015 Two-component Systems similarity (1)

Deposited unit

AAA: Isoform 2 of Ectonucleotide pyrophosphatase/phosphodiesterase family member 2

hetero molecules

91.6 kDa, 1 polymers
Search similar-shape structures of this assembly by Omokage search (details)

1

Idetical with deposited unit
defined by author

Unit cell

Length a, b, c (Å)	61.570, 87.149, 145.361
Angle α, β, γ (deg.)	90.000, 90.000, 90.000
Int Tables number	19
Space group name H-M	P2₁2₁2₁

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Protein , 1 types, 1 molecules AAA

#1: Protein	Isoform 2 of Ectonucleotide pyrophosphatase/phosphodiesterase family member 2 / E-NPP 2 / Autotaxin / Extracellular lysophospholipase D / LysoPLD Mass: 88616.508 Da / Num. of mol.: 1 / Mutation: N53A,N410A,N806A Source method: isolated from a genetically manipulated source Source: (gene. exp.) Rattus norvegicus (Norway rat) / Gene: Enpp2, Atx, Npps2 / Cell line (production host): HEK293T / Production host: Homo sapiens (human) References: UniProt: Q64610, alkylglycerophosphoethanolamine phosphodiesterase

#1: Protein

Isoform 2 of Ectonucleotide pyrophosphatase/phosphodiesterase family member 2 / E-NPP 2 / Autotaxin / Extracellular lysophospholipase D / LysoPLD

Mass: 88616.508 Da / Num. of mol.: 1 / Mutation: N53A,N410A,N806A
Source method: isolated from a genetically manipulated source
Source: (gene. exp.)

Rattus norvegicus (Norway rat) / Gene: Enpp2, Atx, Npps2 / Cell line (production host): HEK293T / Production host:

Homo sapiens (human)
References: UniProt: Q64610, alkylglycerophosphoethanolamine phosphodiesterase

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Sugars , 2 types, 2 molecules

#2: Polysaccharide

alpha-D-mannopyranose-(1-2)-alpha-D-mannopyranose-(1-3)-[alpha-D-mannopyranose-(1-6)]alpha-D- ...

Type: oligosaccharide / Mass: 1194.053 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source

Descriptor	Type	Program
DManpa1-2DManpa1-3[DManpa1-6]DManpa1-6[DManpa1-3]DManpb1-4DGlcpNAcb1-ROH	Glycam Condensed Sequence	GMML 1.0
WURCS=2.0/3,7,6/[a2122h-1b_1-5_2*NCC/3=O][a1122h-1b_1-5][a1122h-1a_1-5]/1-2-3-3-3-3-3/a4-b1_b3-c1_b6-d1_d3-e1_d6-g1_e2-f1	WURCS	PDB2Glycan 1.1.0
[][D-1-deoxy-GlcpNAc]{[(4+1)][b-D-Manp]{[(3+1)][a-D-Manp]{}[(6+1)][a-D-Manp]{[(3+1)][a-D-Manp]{[(2+1)][a-D-Manp]{}}[(6+1)][a-D-Manp]{}}}}	LINUCS	PDB-CARE

#3: 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.: 1 / Source method: obtained synthetically / 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

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Non-polymers , 6 types, 316 molecules

#4: Chemical	ChemComp-SCN / THIOCYANATE ION Mass: 58.082 Da / Num. of mol.: 3 / Source method: obtained synthetically / Formula: CNS
#5: Chemical	ChemComp-ZN / ZINC ION Mass: 65.409 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: Zn
#6: Chemical	ChemComp-CA / CALCIUM ION Mass: 40.078 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: Ca
#7: Chemical	ChemComp-IOD / IODIDE ION Mass: 126.904 Da / Num. of mol.: 5 / Source method: obtained synthetically / Formula: I
#8: Chemical	ChemComp-4I0 / 2-[[2-ethyl-6-[4-[2-[(3~{R})-3-fluoranylpyrrolidin-1-yl]-2-oxidanylidene-ethyl]piperazin-1-yl]imidazo[1,2-a]pyridin-3-yl]-methyl-amino]-4-(4-fluorophenyl)-2,3-dihydro-1,3-thiazole-5-carbonitrile Mass: 592.706 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C₃₀H₃₄F₂N₈OS / Feature type: SUBJECT OF INVESTIGATION
#9: Water	ChemComp-HOH / water Mass: 18.015 Da / Num. of mol.: 304 / Source method: isolated from a natural source / Formula: H₂O

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Details

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: 2.2 Å³/Da / Density % sol: 44.15 %
Crystal grow	Temperature: 298 K / Method: vapor diffusion, hanging drop / Details: PEG3350, NaSCN, NH4I

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Data collection

Diffraction

Mean temperature: 100 K / Serial crystal experiment: N

Diffraction source

Source:

SYNCHROTRON / Site:

SLS

/ Beamline: X06DA / Wavelength: 0.999998 Å

Detector

Type: DECTRIS PILATUS 2M-F / Detector: PIXEL / Date: Jun 15, 2019

Radiation

Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray

Radiation wavelength

Wavelength: 0.999998 Å / Relative weight: 1

Reflection

Resolution: 2.2→48.45 Å / Num. obs: 39684 / % possible obs: 98.4 % / Redundancy: 5.4 % / CC_1/2: 0.977 / R_merge(I) obs: 0.193 / R_pim(I) all: 0.13 / R_rim(I) all: 0.234 / Net I/σ(I): 4.6

Reflection shell

Diffraction-ID: 1

Resolution (Å)	Redundancy (%)	R_merge(I) obs	Num. unique obs	CC_1/2	R_pim(I) all	R_rim(I) all
9.07-48.45	5.4	0.106	624	0.983	0.066	0.125
2.2-2.27	5.3	1.029	3416	0.656	0.694	1.248

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Processing

Software

Name	Version	Classification
REFMAC	5.8.0267	refinement
REFMAC	5.8.0267	refinement
Coot		model building
XDS		data reduction
Aimless		data scaling
MOLREP		phasing

Refinement

Method to determine structure:

MOLECULAR REPLACEMENT
Starting model: 2xr9

2xr9

Resolution: 2.2→47.568 Å / Cor.coef. F_o:F_c: 0.943 / Cor.coef. F_o:F_c free: 0.907 / WR_factor R_free: 0.289 / WR_factor R_work: 0.223 / SU B: 20.219 / SU ML: 0.244 / Average fsc free: 0.8462 / Average fsc work: 0.8687 / Cross valid method: FREE R-VALUE / ESU R: 0.374 / ESU R Free: 0.257
Details: Hydrogens have been added in their riding positions

	R_factor	Num. reflection	% reflection
R_free	0.2708	1926	4.859 %
R_work	0.2124	37715	-
all	0.215	-	-
obs	-	39641	97.913 %

Solvent computation

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

Displacement parameters

B_iso mean: 34.843 Å²

	B_aniso -1	B_aniso -2	B_aniso -3
1-	-0.97 Å²	0 Å²	0 Å²
2-	-	2.433 Å²	-0 Å²
3-	-	-	-1.463 Å²

Refinement step

Cycle: LAST / Resolution: 2.2→47.568 Å

	Protein	Nucleic acid	Ligand	Solvent	Total
Num. atoms	6221	0	153	304	6678

Refine LS restraints

Refine-ID	Type	Dev ideal	Dev ideal target	Number
X-RAY DIFFRACTION	r_bond_refined_d	0.006	0.013	6581
X-RAY DIFFRACTION	r_bond_other_d	0.001	0.014	5926
X-RAY DIFFRACTION	r_angle_refined_deg	1.337	1.677	8929
X-RAY DIFFRACTION	r_angle_other_deg	1.148	1.597	13725
X-RAY DIFFRACTION	r_dihedral_angle_1_deg	7.09	5	769
X-RAY DIFFRACTION	r_dihedral_angle_2_deg	31.573	21.354	362
X-RAY DIFFRACTION	r_dihedral_angle_3_deg	12.777	15	1062
X-RAY DIFFRACTION	r_dihedral_angle_4_deg	14.723	15	48
X-RAY DIFFRACTION	r_chiral_restr	0.052	0.2	838
X-RAY DIFFRACTION	r_gen_planes_refined	0.005	0.02	7302
X-RAY DIFFRACTION	r_gen_planes_other	0.001	0.02	1542
X-RAY DIFFRACTION	r_nbd_refined	0.187	0.2	1345
X-RAY DIFFRACTION	r_symmetry_nbd_other	0.177	0.2	5847
X-RAY DIFFRACTION	r_nbtor_refined	0.164	0.2	3165
X-RAY DIFFRACTION	r_symmetry_nbtor_other	0.084	0.2	2733
X-RAY DIFFRACTION	r_xyhbond_nbd_refined	0.158	0.2	349
X-RAY DIFFRACTION	r_symmetry_xyhbond_nbd_other	0.023	0.2	2
X-RAY DIFFRACTION	r_metal_ion_refined	0.131	0.2	8
X-RAY DIFFRACTION	r_symmetry_nbd_refined	0.172	0.2	24
X-RAY DIFFRACTION	r_nbd_other	0.191	0.2	78
X-RAY DIFFRACTION	r_symmetry_xyhbond_nbd_refined	0.146	0.2	7
X-RAY DIFFRACTION	r_mcbond_it	1.853	2.501	3082
X-RAY DIFFRACTION	r_mcbond_other	1.832	2.498	3078
X-RAY DIFFRACTION	r_mcangle_it	2.82	3.743	3841
X-RAY DIFFRACTION	r_mcangle_other	2.821	3.744	3842
X-RAY DIFFRACTION	r_scbond_it	2.187	2.758	3499
X-RAY DIFFRACTION	r_scbond_other	2.186	2.758	3499
X-RAY DIFFRACTION	r_scangle_it	3.288	4.044	5086
X-RAY DIFFRACTION	r_scangle_other	3.288	4.045	5087
X-RAY DIFFRACTION	r_lrange_it	5.065	29.867	7394
X-RAY DIFFRACTION	r_lrange_other	5.041	29.731	7355

LS refinement shell

Resolution (Å)	R_factor R_free	Num. reflection R_free	R_factor R_work	Num. reflection R_work	Refine-ID	% reflection obs (%)
2.2-2.257	0.33	150	0.311	2738	X-RAY DIFFRACTION	99.1418
2.257-2.319	0.32	150	0.283	2707	X-RAY DIFFRACTION	98.9951
2.319-2.386	0.32	121	0.275	2640	X-RAY DIFFRACTION	99.2808
2.386-2.46	0.291	115	0.253	2613	X-RAY DIFFRACTION	99.0559
2.46-2.54	0.318	145	0.242	2451	X-RAY DIFFRACTION	98.5948
2.54-2.629	0.263	118	0.227	2375	X-RAY DIFFRACTION	98.6936
2.629-2.729	0.277	128	0.216	2335	X-RAY DIFFRACTION	98.3233
2.729-2.84	0.31	105	0.211	2231	X-RAY DIFFRACTION	98.6487
2.84-2.966	0.258	131	0.214	2128	X-RAY DIFFRACTION	98.4743
2.966-3.111	0.305	105	0.207	2037	X-RAY DIFFRACTION	97.4522
3.111-3.279	0.226	87	0.2	1962	X-RAY DIFFRACTION	98.2734
3.279-3.478	0.258	85	0.205	1850	X-RAY DIFFRACTION	97.334
3.478-3.718	0.254	85	0.197	1705	X-RAY DIFFRACTION	96.9139
3.718-4.016	0.275	80	0.202	1628	X-RAY DIFFRACTION	97.0455
4.016-4.398	0.262	68	0.166	1509	X-RAY DIFFRACTION	96.8673
4.398-4.917	0.215	70	0.149	1341	X-RAY DIFFRACTION	96.8428
4.917-5.677	0.354	72	0.226	1198	X-RAY DIFFRACTION	96.2851
5.677-6.95	0.236	46	0.225	1009	X-RAY DIFFRACTION	94.2806
6.95-9.817	0.179	44	0.176	787	X-RAY DIFFRACTION	93.0571
9.817-40	0.225	21	0.224	472	X-RAY DIFFRACTION	92.4953

Refinement TLS params.

Method: refined / Origin x: -4.3383 Å / Origin y: 0.0555 Å / Origin z: -9.3854 Å

	11	12	13	21	22	23	31	32	33
T	0.0209 Å²	0.0089 Å²	0.0056 Å²	-	0.0625 Å²	0.0057 Å²	-	-	0.0019 Å²
L	0.439 °²	0.0368 °²	0.2184 °²	-	0.4372 °²	0.3013 °²	-	-	1.709 °²
S	0.0023 Å °	-0.0304 Å °	-0.0103 Å °	0.0366 Å °	-0.02 Å °	0.009 Å °	0.0675 Å °	-0.0384 Å °	0.0178 Å °

Refinement TLS group

ID	Refine-ID	Refine TLS-ID	Selection	Auth asym-ID	Auth seq-ID
1	X-RAY DIFFRACTION	1	ALL	AAA	56 - 859
2	X-RAY DIFFRACTION	1	ALL	AaA	1902
3	X-RAY DIFFRACTION	1	ALL	AbA	2310
4	X-RAY DIFFRACTION	1	ALL	AcA	1863
5	X-RAY DIFFRACTION	1	ALL	AdA	1866
6	X-RAY DIFFRACTION	1	ALL	AeA	1867
7	X-RAY DIFFRACTION	1	ALL	AfA	1868
8	X-RAY DIFFRACTION	1	ALL	AgA	1869
9	X-RAY DIFFRACTION	1	ALL	AhA	1871
10	X-RAY DIFFRACTION	1	ALL	AiA	1875
11	X-RAY DIFFRACTION	1	ALL	AjA	1893
12	X-RAY DIFFRACTION	1	ALL	AkA	1901
13	X-RAY DIFFRACTION	1	ALL	AlA	2305
14	X-RAY DIFFRACTION	1	ALL	AmA	2306
15	X-RAY DIFFRACTION	1	ALL	AnA	2309
16	X-RAY DIFFRACTION	1	ALL	AoA	2311
17	X-RAY DIFFRACTION	1	ALL	ApA	2312
18	X-RAY DIFFRACTION	1	ALL	AqA	2313
19	X-RAY DIFFRACTION	1	ALL	ArA	2314
20	X-RAY DIFFRACTION	1	ALL	AsA	2315

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