PDB-2wj2: 3D-crystal structure of humanized-rat fatty acid amide hydrolase ...

ID or keywords:

Entry

Database: PDB / ID: 2wj2

Title

3D-crystal structure of humanized-rat fatty acid amide hydrolase (FAAH) conjugated with 7-phenyl-1-(5-(pyridin-2-yl)oxazol-2-yl)heptan- 1-one, an alpha-ketooxazole

Components

FATTY ACID AMIDE HYDROLASE 1

Keywords

HYDROLASE / ENDOPLASMIC RETICULUM / MONOTOPIC MEMBRANE PROTEIN / MEMBRANE / TRANSMEMBRANE / PHOSPHOPROTEIN / COVALENT REVERSIBLE INHIBITORS / FATTY ACID AMIDE HYDROLASE / GOLGI APPARATUS / ALPHA-KETOOXAZOLE

Function / homology

Function and homology information

Arachidonic acid metabolism / fatty acid amide hydrolase / fatty acid amide hydrolase activity / monoacylglycerol catabolic process / monoacylglycerol lipase activity / amidase activity / fatty acid catabolic process / Hydrolases; Acting on ester bonds; Carboxylic-ester hydrolases / hydrolase activity, acting on ester bonds / organelle membrane ...
Similarity search - Function

Biological species

RATTUS NORVEGICUS (Norway rat)

Method

X-RAY DIFFRACTION /

SYNCHROTRON /

MOLECULAR REPLACEMENT / Resolution: 2.55 Å

Authors

Mileni, M. / Garfunkle, J. / DeMartino, J.K. / Cravatt, B.F. / Boger, D.L. / Stevens, R.C.

Citation

Journal: J.Am.Chem.Soc. / Year: 2009
Title: Binding and Inactivation Mechanism of a Humanized Fatty Acid Amide Hydrolase by Alpha-Ketoheterocycle Inhibitors Revealed from Cocrystal Structures.
Authors: Mileni, M. / Garfunkle, J. / Demartino, J.K. / Cravatt, B.F. / Boger, D.L. / Stevens, R.C.

History

Deposition	May 19, 2009	Deposition site: PDBE / Processing site: PDBE
Revision 1.0	Sep 15, 2009	Provider: repository / Type: Initial release
Revision 1.1	May 8, 2011	Group: Version format compliance
Revision 1.2	Jul 13, 2011	Group: Version format compliance
Revision 1.3	Dec 13, 2023	Group: Data collection / Database references ...Data collection / Database references / Derived calculations / Other / Refinement description Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / database_2 / pdbx_database_status / pdbx_initial_refinement_model / struct_conn / struct_site Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession ..._database_2.pdbx_DOI / _database_2.pdbx_database_accession / _pdbx_database_status.status_code_sf / _struct_conn.pdbx_leaving_atom_flag / _struct_site.pdbx_auth_asym_id / _struct_site.pdbx_auth_comp_id / _struct_site.pdbx_auth_seq_id

Structure viewer	Molecule: MolmilJmol/JSmol

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Download

PDBx/mmCIF format	2wj2.cif.gz	423 KB	Display	PDBx/mmCIF format
PDB format	pdb2wj2.ent.gz	347.5 KB	Display	PDB format
PDBx/mmJSON format	2wj2.json.gz		Tree view	PDBx/mmJSON format
Others	Other downloads

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Validation report

Summary document	2wj2_validation.pdf.gz	889.8 KB	Display	wwPDB validaton report
Full document	2wj2_full_validation.pdf.gz	901 KB	Display
Data in XML	2wj2_validation.xml.gz	39.5 KB	Display
Data in CIF	2wj2_validation.cif.gz	55.9 KB	Display
Arichive directory	https://data.pdbj.org/pub/pdb/validation_reports/wj/2wj2 ftp://data.pdbj.org/pub/pdb/validation_reports/wj/2wj2	HTTPS FTP

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Related structure data

Related structure data	2wj1C 2vyaS 1mt5 2wap S: Starting model for refinement C: citing same article (ref.)
Similar structure data	3lj6-d 3k7f-d 3k83-d 3lj7-d 3qj8-d 3ppm-d 3k84-d 4do3-d 1mt5-5 3qj9-d Search similar-shape structures by Omokage search (details) 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

A: FATTY ACID AMIDE HYDROLASE 1

B: FATTY ACID AMIDE HYDROLASE 1

hetero molecules

127 kDa, 2 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)	103.440, 103.440, 254.130
Angle α, β, γ (deg.)	90.00, 90.00, 120.00
Int Tables number	154
Space group name H-M	P3₂21

Noncrystallographic symmetry (NCS)

NCS domain:

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

NCS domain segments:

Dom-ID	Component-ID	Ens-ID	Selection details
1	1	1	CHAIN A AND (RESSEQ 33:72 )
2	1	1	CHAIN B AND (RESSEQ 33:72 )
1	1	2	CHAIN A AND (RESSEQ 73:139 )
2	1	2	CHAIN B AND (RESSEQ 73:139 )
1	1	3	CHAIN A AND (RESSEQ 140:242 )
2	1	3	CHAIN B AND (RESSEQ 140:242 )
1	1	4	CHAIN A AND (RESSEQ 243:315 )
2	1	4	CHAIN B AND (RESSEQ 243:315 )
1	1	5	CHAIN A AND (RESSEQ 316:415 )
2	1	5	CHAIN B AND (RESSEQ 316:415 )
1	1	6	CHAIN A AND (RESSEQ 416:577 )
2	1	6	CHAIN B AND (RESSEQ 416:577 )

NCS ensembles :

ID
1
2
3
4
5
6

NCS oper: (Code: given
Matrix: (-0.9308, -0.3635, -0.0387), (-0.3638, 0.911, 0.1943), (-0.0354, 0.1949, -0.9802)
Vector: 49.5352, 3.7663, 57.4344)

#1: Protein	FATTY ACID AMIDE HYDROLASE 1 / FATTY ACID AMIDE HYDROLASE / OLEAMIDE HYDROLASE 1 / ANANDAMIDE AMIDOHYDROLASE 1 Mass: 63111.664 Da / Num. of mol.: 2 / Fragment: RESIDUES 30-579 / Mutation: YES Source method: isolated from a genetically manipulated source Source: (gene. exp.) RATTUS NORVEGICUS (Norway rat) / Production host: ESCHERICHIA COLI (E. coli) / Strain (production host): BL21 A.I. / References: UniProt: P97612, amidase
#2: Chemical	ChemComp-OL1 / 7-phenyl-1-(5-pyridin-2-yl-1,3-oxazol-2-yl)heptane-1,1-diol Mass: 352.427 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C₂₁H₂₄N₂O₃
#3: Chemical	ChemComp-CL / CHLORIDE ION Mass: 35.453 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: Cl
#4: Water	ChemComp-HOH / water Mass: 18.015 Da / Num. of mol.: 186 / Source method: isolated from a natural source / Formula: H₂O
Compound details	ENGINEERED RESIDUE IN CHAIN A, LEU 192 TO PHE ENGINEERED RESIDUE IN CHAIN A, PHE 194 TO TYR ...ENGINEERED RESIDUE IN CHAIN A, LEU 192 TO PHE ENGINEERED RESIDUE IN CHAIN A, PHE 194 TO TYR ENGINEERED RESIDUE IN CHAIN A, ALA 377 TO THR ENGINEERED RESIDUE IN CHAIN A, SER 435 TO ASN ENGINEERED RESIDUE IN CHAIN A, ILE 491 TO VAL ENGINEERED RESIDUE IN CHAIN A, VAL 495 TO MET ENGINEERED RESIDUE IN CHAIN B, LEU 192 TO PHE ENGINEERED RESIDUE IN CHAIN B, PHE 194 TO TYR ENGINEERED RESIDUE IN CHAIN B, ALA 377 TO THR ENGINEERED RESIDUE IN CHAIN B, SER 435 TO ASN ENGINEERED RESIDUE IN CHAIN B, ILE 491 TO VAL ENGINEERED RESIDUE IN CHAIN B, VAL 495 TO MET
Nonpolymer details	7-PHENYL-1-(5-(PYRIDIN-2-YL)OXAZOL-2-YL)HEPTAN-1-ONE (OL1): THE CARBONYL CARBON OF THE ABOVE ...7-PHENYL-1-(5-(PYRIDIN-2-YL)OXAZOL-2-YL)HEPTAN-1-ONE (OL1): THE CARBONYL CARBON OF THE ABOVE INHIBITOR COVALENTLY ATTACHES TO SER241 FORMING A TETRAHEDRAL CARBON AND AN OLATE

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Experiment

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

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Sample preparation

Crystal	Density Matthews: 3 Å³/Da / Density % sol: 59 % / Description: NONE
Crystal grow	pH: 7.5 / Details: pH 7.5

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Data collection

Diffraction	Mean temperature: 100 K
Diffraction source	Source: SYNCHROTRON / Site: SSRL / Beamline: BL11-1 / Wavelength: 0.97945
Detector	Type: MARRESEARCH / Detector: CCD / Date: Nov 21, 2008
Radiation	Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelength	Wavelength: 0.97945 Å / Relative weight: 1
Reflection	Resolution: 2.55→30 Å / Num. obs: 52071 / % possible obs: 99 % / Observed criterion σ(I): -3 / Redundancy: 4.3 % / B_iso Wilson estimate: 24.74 Å² / R_merge(I) obs: 0.16 / Net I/σ(I): 9.2
Reflection shell	Resolution: 2.55→2.62 Å / Redundancy: 4.3 % / R_merge(I) obs: 0.68 / Mean I/σ(I) obs: 2.3 / % possible all: 99

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Processing

Software

Name	Version	Classification
PHENIX	(PHENIX.REFINE)	refinement
XDS		data reduction
XSCALE		data scaling
PHASER		phasing

Refinement

Method to determine structure:

MOLECULAR REPLACEMENT
Starting model: PDB ENTRY 2VYA

2vya

Resolution: 2.55→29.88 Å / SU ML: 0.36 / σ(F): 1.99 / Phase error: 21.65 / Stereochemistry target values: ML / Details: RESIDUES 1-32 AND 579 ARE DISORDERED

	R_factor	Num. reflection	% reflection
R_free	0.235	2622	5 %
R_work	0.1838	-	-
obs	0.1864	52071	99.63 %

Solvent computation

Shrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL / B_sol: 26.911 Å² / k_sol: 0.347 e/Å³

Displacement parameters

B_iso mean: 25.9 Å²

	B_aniso -1	B_aniso -2	B_aniso -3
1-	2.0316 Å²	0 Å²	-0 Å²
2-	-	2.0316 Å²	0 Å²
3-	-	-	-4.0632 Å²

Refinement step

Cycle: LAST / Resolution: 2.55→29.88 Å

	Protein	Nucleic acid	Ligand	Solvent	Total
Num. atoms	8421	0	51	186	8658

Refine LS restraints

Refine-ID	Type	Dev ideal	Number
X-RAY DIFFRACTION	f_bond_d	0.014	8678
X-RAY DIFFRACTION	f_angle_d	1.45	11774
X-RAY DIFFRACTION	f_dihedral_angle_d	21.138	3232
X-RAY DIFFRACTION	f_chiral_restr	0.08	1313
X-RAY DIFFRACTION	f_plane_restr	0.006	1520

Refine LS restraints NCS

Ens-ID	Dom-ID	Auth asym-ID	Number	Refine-ID	Type	Rms dev position (Å)
1	1	A	320	X-RAY DIFFRACTION	POSITIONAL
1	2	B	320	X-RAY DIFFRACTION	POSITIONAL	0.756
2	1	A	516	X-RAY DIFFRACTION	POSITIONAL
2	2	B	516	X-RAY DIFFRACTION	POSITIONAL	0.523
3	1	A	735	X-RAY DIFFRACTION	POSITIONAL
3	2	B	735	X-RAY DIFFRACTION	POSITIONAL	0.429
4	1	A	544	X-RAY DIFFRACTION	POSITIONAL
4	2	B	544	X-RAY DIFFRACTION	POSITIONAL	0.586
5	1	A	801	X-RAY DIFFRACTION	POSITIONAL
5	2	B	801	X-RAY DIFFRACTION	POSITIONAL	0.507
6	1	A	1296	X-RAY DIFFRACTION	POSITIONAL
6	2	B	1296	X-RAY DIFFRACTION	POSITIONAL	0.969

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 (%)
2.55-2.5964	0.2678	156	0.2139	2564	X-RAY DIFFRACTION	100
2.5964-2.6463	0.3106	141	0.2132	2572	X-RAY DIFFRACTION	100
2.6463-2.7002	0.2761	142	0.2151	2536	X-RAY DIFFRACTION	100
2.7002-2.7589	0.3337	130	0.2186	2571	X-RAY DIFFRACTION	100
2.7589-2.8231	0.2921	127	0.22	2606	X-RAY DIFFRACTION	100
2.8231-2.8936	0.2807	138	0.2192	2575	X-RAY DIFFRACTION	100
2.8936-2.9718	0.2852	124	0.2191	2573	X-RAY DIFFRACTION	100
2.9718-3.0591	0.2956	151	0.2198	2573	X-RAY DIFFRACTION	100
3.0591-3.1578	0.2663	141	0.2095	2583	X-RAY DIFFRACTION	100
3.1578-3.2705	0.2465	129	0.1983	2592	X-RAY DIFFRACTION	100
3.2705-3.4013	0.2531	134	0.1948	2579	X-RAY DIFFRACTION	100
3.4013-3.5558	0.245	135	0.1741	2638	X-RAY DIFFRACTION	100
3.5558-3.743	0.1854	141	0.1553	2586	X-RAY DIFFRACTION	100
3.743-3.977	0.204	127	0.1537	2643	X-RAY DIFFRACTION	100
3.977-4.2832	0.2386	143	0.1529	2602	X-RAY DIFFRACTION	100
4.2832-4.7128	0.169	136	0.1448	2642	X-RAY DIFFRACTION	100
4.7128-5.3912	0.1665	153	0.1455	2634	X-RAY DIFFRACTION	100
5.3912-6.7793	0.2008	144	0.1735	2648	X-RAY DIFFRACTION	99
6.7793-29.8823	0.1768	130	0.1576	2732	X-RAY DIFFRACTION	96

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	0.2744	0.0591	-0.0966	0.3603	0.1765	0.5273	-0.0323	0.3991	0.2257	-0.2316	0.0018	0.1511	-0.5022	-0.1894	0.0452	0.176	-0.0165	-0.0783	0.2305	0.0046	0.0885	23.3365	-32.3212	-14.3786
2	0.0846	0.0393	0.0519	0.0929	0.0046	0.0652	-0.1027	0.1413	0.1805	-0.224	-0.0041	0.3232	-0.148	-0.1256	-0.0027	0.1628	0.0298	-0.0095	0.2051	0.0458	0.2197	24.3864	-19.3925	-4.5657
3	0.0462	0.017	0.0377	0.0678	0.1292	0.1041	-0.0108	0.1585	-0.0431	-0.1436	0.0139	0.079	-0.0631	-0.1778	-0.0002	0.0716	-0.0067	-0.0133	0.1666	0.0177	0.1026	30.4812	-34.9802	-0.4123
4	0.0565	0.0023	-0.0059	0.0013	0.0419	0.2135	-0.0141	0.1259	0.0257	0.0441	0.0322	0.0432	-0.0905	-0.2045	-0.0718	0.0672	0.0266	0.0155	0.0851	0.04	0.0415	31.9024	-28.8709	12.3862
5	0.0983	-0.0533	-0.1426	0.1603	-0.1161	0.3288	0.0215	-0.0157	-0.039	0.0109	-0.0746	-0.0934	-0.0062	0.0967	-0.0313	0.0251	0.0063	0.0056	0.0607	0.0053	0.0595	48.1099	-36.8351	10.9715
6	0.1578	-0.0511	0.1237	0.1254	0.0623	0.1859	-0.0141	0.0656	-0.0144	-0.0248	-0.0008	-0.0566	-0.0162	0.0995	-0.0582	0.0431	0.0068	0.0249	0.0859	-0.0034	0.0392	49.8662	-35.5521	10.487
7	0.1767	0.0014	-0.1433	0.1709	-0.0737	0.399	-0.1581	-0.0801	-0.3946	-0.169	-0.2304	-0.0547	0.3085	0.0922	-0.2332	-0.1077	-0.0135	-0.2006	0.1166	-0.0184	-0.1479	39.8635	-37.3357	64.4593
8	0.1438	0.0434	0.0378	0.0776	-0.04	0.1364	-0.1641	-0.1338	-0.0169	-0.064	0.0494	-0.1361	-0.0321	-0.033	-0.0878	-0.0145	-0.086	-0.0574	-0.0218	-0.0705	-0.0015	33.9494	-24.0544	57.1756
9	0.0392	-0.023	0.0357	0.0114	-0.0414	-0.0168	-0.0073	-0.0214	0.0021	0.0192	0.0326	0.0234	0.0025	0.0183	0	0.0393	-0.0073	0.004	0.0633	0.0115	0.0702	33.842	-39.7067	49.9158
10	0.0292	0.0098	-0.0163	0.0243	-0.0476	0.0685	-0.0551	-0.0281	-0.0419	-0.071	0.0591	0.0462	0.0382	0.015	0	0.1385	-0.0132	0.0102	0.1093	0.0141	0.12	29.8181	-31.9848	38.5089
11	0.1857	0.1801	-0.1225	0.0792	-0.0479	0.3589	0.0131	0.0886	-0.0222	-0.0503	-0.0182	-0.0296	0.3152	-0.1709	0.026	-0.2037	0.0054	0.023	0.0443	-0.0275	0.0856	17.7908	-45.5584	37.7623
12	0.3248	0.1759	-0.0128	0.2155	-0.0407	0.1248	0.0033	0.0286	0.007	-0.1035	0.0134	0.0261	-0.0042	-0.0982	-0.0486	0.0142	-0.0111	0.0191	0.0619	0.0069	0.0375	15.7252	-45.2323	38.2275

Refinement TLS group

ID	Refine-ID	Refine TLS-ID	Selection details
1	X-RAY DIFFRACTION	1	(CHAIN A AND RESID 33:72)
2	X-RAY DIFFRACTION	2	(CHAIN A AND RESID 73:139)
3	X-RAY DIFFRACTION	3	(CHAIN A AND RESID 140:242)
4	X-RAY DIFFRACTION	4	(CHAIN A AND RESID 243:315)
5	X-RAY DIFFRACTION	5	(CHAIN A AND RESID 316:415)
6	X-RAY DIFFRACTION	6	(CHAIN A AND RESID 416:578)
7	X-RAY DIFFRACTION	7	(CHAIN B AND RESID 33:72)
8	X-RAY DIFFRACTION	8	(CHAIN B AND RESID 73:139)
9	X-RAY DIFFRACTION	9	(CHAIN B AND RESID 140:242)
10	X-RAY DIFFRACTION	10	(CHAIN B AND RESID 243:315)
11	X-RAY DIFFRACTION	11	(CHAIN B AND RESID 316:415)
12	X-RAY DIFFRACTION	12	(CHAIN B AND RESID 416:577)

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