PDB-2wj1: 3D-crystal structure of humanized-rat fatty acid amide hydrolase ...

ID or keywords:

Entry

Database: PDB / ID: 2wj1

Title

3D-crystal structure of humanized-rat fatty acid amide hydrolase (FAAH) conjugated with 7-phenyl-1-(4-(pyridin-2-yl)oxazol-2-yl)heptan- 1-one, an alpha-ketooxazole

Components

FATTY-ACID AMIDE HYDROLASE 1

Keywords

HYDROLASE / MONOTOPIC MEMBRANE PROTEIN /

FATTY ACID AMIDE HYDROLASE /

GOLGI APPARATUS /

ENDOPLASMIC RETICULUM /

MEMBRANE /

TRANSMEMBRANE /

PHOSPHOPROTEIN /

COVALENT REVERSIBLE INHIBITOR

Function / homology

Function and homology information

Arachidonic acid metabolism /

fatty acid amide hydrolase /

fatty acid amide hydrolase activity / monoacylglycerol catabolic process /

acylglycerol 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: 1.84 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	2wj1.cif.gz	437.9 KB	Display	PDBx/mmCIF format
PDB format	pdb2wj1.ent.gz	358.9 KB	Display	PDB format
PDBx/mmJSON format	2wj1.json.gz		Tree view	PDBx/mmJSON format
Others	Other downloads

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Validation report

Arichive directory	https://data.pdbj.org/pub/pdb/validation_reports/wj/2wj1 ftp://data.pdbj.org/pub/pdb/validation_reports/wj/2wj1	HTTPS FTP

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Related structure data

Related structure data	2wj2C 2vyaS 1mt5 2wap S: Starting model for refinement C: citing same article (ref.)
Similar structure data	3oj8-d 1mt5-3 3k84-d 3qkv-d 4hbp-d 1mt5-5 1mt5-4 3qj8-d 3qj9-d 1mt5-1 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)	75.830, 106.210, 79.390
Angle α, β, γ (deg.)	90.00, 100.20, 90.00
Int Tables number	4
Space group name H-M	P12₁1

Noncrystallographic symmetry (NCS)

NCS domain:
NCS domain segments:
NCS ensembles :

ID
1
2
3
4
5
6
7
8

NCS oper: (Code: given
Matrix: (0.2372, -0.0126, -0.9714), (-0.0163, -0.9998, 0.009), (-0.9713, 0.0137, -0.2373)
Vector: 30.421, -51.27, 39.5068)

#1: Protein	FATTY-ACID AMIDE HYDROLASE 1 / OLEAMIDE HYDROLASE 1 / ANANDAMIDE AMIDOHYDROLASE 1 / FATTY ACID AMIDE HYDROLASE 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-S99 / 7-phenyl-1-(4-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 / Chloride Mass: 35.453 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: Cl
#4: Water	ChemComp-HOH / water / Water Mass: 18.015 Da / Num. of mol.: 625 / 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-(4-(PYRIDIN-2-YL)OXAZOL-2-YL)HEPTAN-1-ONE (DRG): THE CARBONYL CARBON OF THE ABOVE ...7-PHENYL-1-(4-(PYRIDIN-2-YL)OXAZOL-2-YL)HEPTAN-1-ONE (DRG): 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: 2.4 Å³/Da / Density % sol: 49 % / 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: APS / Beamline: 23-ID-D / Wavelength: 1.0332
Detector	Type: MARRESEARCH / Detector: CCD / Date: Feb 7, 2009
Radiation	Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelength	Wavelength: 1.0332 Å / Relative weight: 1
Reflection	Resolution: 1.84→36.3 Å / Num. obs: 106195 / % possible obs: 99 % / Observed criterion σ(I): -3 / Redundancy: 3.7 % / B_iso Wilson estimate: 19.89 Å² / R_merge(I) obs: 0.1 / Net I/σ(I): 8.7
Reflection shell	Resolution: 1.84→1.9 Å / Redundancy: 3.7 % / R_merge(I) obs: 0.62 / Mean I/σ(I) obs: 2.1 / % 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: 1.84→36.306 Å / SU ML: 0.22 / σ(F): 1.99 / Phase error: 22.4 / Stereochemistry target values: ML / Details: RESIDUES 1-33 AND 578-579 ARE DISORDERED

	R_factor	Num. reflection	% reflection
R_free	0.2142	5311	5 %
R_work	0.1858	-	-
obs	0.1873	106195	99.13 %

Solvent computation

Shrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL / B_sol: 52.715 Å² / k_sol: 0.357 e/Å³

Displacement parameters

B_iso mean: 30 Å²

	B_aniso -1	B_aniso -2	B_aniso -3
1-	4.9808 Å²	0 Å²	-4.4769 Å²
2-	-	-7.3035 Å²	-0 Å²
3-	-	-	1.4175 Å²

Refinement step

Cycle: LAST / Resolution: 1.84→36.306 Å

	Protein	Nucleic acid	Ligand	Solvent	Total
Num. atoms	8397	0	51	625	9073

Refine LS restraints

Refine-ID	Type	Dev ideal	Number
X-RAY DIFFRACTION	f_bond_d	0.014	8653
X-RAY DIFFRACTION	f_angle_d	1.469	11740
X-RAY DIFFRACTION	f_dihedral_angle_d	20.35	3222
X-RAY DIFFRACTION	f_chiral_restr	0.104	1309
X-RAY DIFFRACTION	f_plane_restr	0.007	1514

Refine LS restraints NCS

Ens-ID	Dom-ID	Auth asym-ID	Number	Refine-ID	Type	Rms dev position (Å)
1	1	A	301	X-RAY DIFFRACTION	POSITIONAL
1	2	B	301	X-RAY DIFFRACTION	POSITIONAL	0.82
2	1	A	494	X-RAY DIFFRACTION	POSITIONAL
2	2	B	494	X-RAY DIFFRACTION	POSITIONAL	0.497
3	1	A	233	X-RAY DIFFRACTION	POSITIONAL
3	2	B	233	X-RAY DIFFRACTION	POSITIONAL	0.45
4	1	A	783	X-RAY DIFFRACTION	POSITIONAL
4	2	B	783	X-RAY DIFFRACTION	POSITIONAL	0.266
5	1	A	300	X-RAY DIFFRACTION	POSITIONAL
5	2	B	300	X-RAY DIFFRACTION	POSITIONAL	0.778
6	1	A	754	X-RAY DIFFRACTION	POSITIONAL
6	2	B	754	X-RAY DIFFRACTION	POSITIONAL	0.555
7	1	A	351	X-RAY DIFFRACTION	POSITIONAL
7	2	B	351	X-RAY DIFFRACTION	POSITIONAL	0.677
8	1	A	965	X-RAY DIFFRACTION	POSITIONAL
8	2	B	965	X-RAY DIFFRACTION	POSITIONAL	0.412

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 (%)
1.84-1.8609	0.2631	177	0.2381	3363	X-RAY DIFFRACTION	100
1.8609-1.8828	0.2931	175	0.2278	3324	X-RAY DIFFRACTION	100
1.8828-1.9058	0.2759	174	0.2645	3307	X-RAY DIFFRACTION	98
1.9058-1.9299	0.3503	174	0.3295	3302	X-RAY DIFFRACTION	97
1.9299-1.9553	0.2832	174	0.245	3309	X-RAY DIFFRACTION	99
1.9553-1.9821	0.2379	179	0.1927	3394	X-RAY DIFFRACTION	100
1.9821-2.0104	0.2209	179	0.1869	3393	X-RAY DIFFRACTION	100
2.0104-2.0404	0.2155	179	0.1916	3397	X-RAY DIFFRACTION	100
2.0404-2.0723	0.2463	175	0.2205	3341	X-RAY DIFFRACTION	99
2.0723-2.1062	0.2424	177	0.2	3361	X-RAY DIFFRACTION	99
2.1062-2.1425	0.2115	178	0.1853	3371	X-RAY DIFFRACTION	100
2.1425-2.1815	0.2157	176	0.178	3354	X-RAY DIFFRACTION	100
2.1815-2.2235	0.2141	177	0.1938	3367	X-RAY DIFFRACTION	99
2.2235-2.2688	0.3456	168	0.2892	3186	X-RAY DIFFRACTION	94
2.2688-2.3182	0.2208	176	0.1944	3343	X-RAY DIFFRACTION	99
2.3182-2.3721	0.2195	180	0.1749	3418	X-RAY DIFFRACTION	100
2.3721-2.4314	0.2209	176	0.1776	3352	X-RAY DIFFRACTION	100
2.4314-2.4971	0.1969	178	0.1739	3377	X-RAY DIFFRACTION	100
2.4971-2.5706	0.2047	177	0.1768	3363	X-RAY DIFFRACTION	99
2.5706-2.6535	0.2256	179	0.1821	3400	X-RAY DIFFRACTION	100
2.6535-2.7483	0.2127	177	0.1818	3357	X-RAY DIFFRACTION	100
2.7483-2.8583	0.2136	177	0.1785	3373	X-RAY DIFFRACTION	100
2.8583-2.9884	0.23	179	0.1843	3396	X-RAY DIFFRACTION	100
2.9884-3.1458	0.2417	179	0.185	3403	X-RAY DIFFRACTION	100
3.1458-3.3428	0.1968	179	0.172	3400	X-RAY DIFFRACTION	100
3.3428-3.6007	0.1895	178	0.1633	3379	X-RAY DIFFRACTION	99
3.6007-3.9626	0.1745	176	0.1636	3350	X-RAY DIFFRACTION	99
3.9626-4.5351	0.1794	180	0.1552	3405	X-RAY DIFFRACTION	100
4.5351-5.7102	0.1664	179	0.1613	3399	X-RAY DIFFRACTION	99
5.7102-36.3126	0.1792	179	0.1769	3400	X-RAY DIFFRACTION	98

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	0.7102	0.1508	0.0623	1.0566	-0.0367	0.8035	0.163	0.5879	0.2566	-0.3995	0.058	0.5677	-0.1732	-0.3612	0.0668	0.2515	0.0188	-0.173	0.3638	0.0762	0.2657	-3.0089	-29.1039	-17.3076
2	0.4386	0.4275	-0.1959	0.926	-0.1727	0.6424	-0.0055	0.3554	0.1463	-0.3549	0.015	0.1735	-0.0277	0.0911	-0.0042	0.2556	-0.0148	-0.0469	0.3352	0.0378	0.1309	12.9961	-30.5645	-17.957
3	0.5268	0.0905	0.2378	0.5019	-0.2823	0.3253	-0.0281	0.0793	0.0867	-0.0978	0.0221	0.2597	-0.0325	-0.0337	-0.0075	0.076	-0.0076	-0.0241	0.1251	0.0015	0.1748	4.3175	-31.6259	-3.1194
4	0.3368	0.1928	0.1332	0.3335	-0.1428	0.1818	0.0121	0.0564	0.039	-0.056	-0.01	0.1276	-0.0369	0.0249	-0	0.1085	0.0003	0.0035	0.1384	-0.0138	0.1392	17.4891	-30.76	2.2875
5	0.5963	-0	0.1489	0.8055	0.0834	0.3784	0.0263	-0.0053	-0.1088	0.0555	-0.019	0.145	0.1034	-0.0103	0	0.1172	-0.0158	0.0312	0.1241	-0.0038	0.1575	11.001	-44.6147	12.1322
6	0.4698	-0.076	-0.1155	0.7976	0.163	0.4611	0.0484	-0.0215	-0.0971	0.0707	-0.0039	0.094	0.1022	0.0117	0.0588	0.0911	-0.0171	0.011	0.0854	-0.0019	0.1204	11.5285	-46.628	12.021
7	0.6195	-0.2032	0.1654	0.9083	0.1322	0.5427	-0.2231	-0.3749	0.0192	0.5666	0.0272	-0.2514	-0.0435	0.4762	-0.0625	0.4646	-0.0186	-0.2003	0.4379	0.0952	0.2518	46.8538	-22.6315	46.1298
8	0.5198	0.0165	-0.1142	0.6346	0.1508	0.3506	-0.0247	-0.1053	-0.0965	0.3813	-0.0838	-0.471	0.1515	0.3627	-0.0127	0.2438	0.0205	-0.1037	0.3019	0.0456	0.3017	51.3865	-21.2816	30.695
9	0.2766	-0.1235	-0.0759	0.2626	0.1419	0.5116	0.0231	-0.0905	-0.0196	0.3462	-0.0157	-0.0912	0.0723	0.077	-0.0001	0.2401	-0.0104	-0.0373	0.1219	0.0126	0.0817	34.8876	-19.878	35.6663
10	0.336	-0.2908	0.0616	0.3694	0.0377	0.4263	-0.0023	-0.0017	-0.0351	0.1255	-0.0449	-0.0603	-0.0096	0.0608	-0	0.1551	-0.0283	-0.0065	0.1442	0.003	0.1289	32.7635	-20.8406	21.6048
11	0.6071	0.2688	0.108	0.9229	0.0326	0.6462	-0.0031	-0.0779	0.1437	0.215	-0.0718	0.0921	-0.1214	-0.0172	-0.0146	0.1705	0.0043	0.0286	0.1152	-0.0238	0.1375	21.8733	-6.7905	25.4176
12	0.6416	0.3736	-0.0634	1.0353	0.0181	0.3137	-0.0258	-0.0258	0.0975	0.1563	-0.0506	0.0855	-0.1375	-0.0106	-0.0648	0.1784	-0.0017	-0.0013	0.1044	-0.0233	0.1237	22.3044	-4.8008	24.8691

Refinement TLS group

ID	Refine-ID	Refine TLS-ID	Selection details
1	X-RAY DIFFRACTION	1	(CHAIN A AND RESID 34:72)
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 416:576)
7	X-RAY DIFFRACTION	7	(CHAIN B AND RESID 34:72)
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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