PDB-3lj6: 3D-CRYSTAL STRUCTURE OF HUMANIZED-RAT FATTY ACID AMIDE HYDROLASE ...

ID or keywords:

Entry

Database: PDB / ID: 3lj6

Title

3D-CRYSTAL STRUCTURE OF HUMANIZED-RAT FATTY ACID AMIDE HYDROLASE (FAAH) CONJUGATED WITH THE DRUG-LIKE UREA INHIBITOR PF-3845 at 2.42A RESOLUTION

Components

Fatty-acid amide hydrolase 1

Keywords

HYDROLASE / protein-inhibitor complex / FAAH /

fatty acid amide hydrolase /

urea /

inhibitor /

covalent /

Endoplasmic reticulum /

Golgi apparatus /

Membrane /

Transmembrane

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: 2.42 Å

Authors

Mileni, M. / Stevens, R.C. / Kamtekar, S.

Citation

Journal: J.Mol.Biol. / Year: 2010
Title: Crystal structure of fatty acid amide hydrolase bound to the carbamate inhibitor URB597: discovery of a deacylating water molecule and insight into enzyme inactivation
Authors: Mileni, M. / Kamtekar, S. / Wood, D.C. / Benson, T.E. / Cravatt, B.F. / Stevens, R.C.

History

Deposition	Jan 25, 2010	Deposition site: RCSB / Processing site: RCSB
Revision 1.0	Jun 9, 2010	Provider: repository / Type: Initial release
Revision 1.1	Jul 13, 2011	Group: Version format compliance
Revision 1.2	Dec 14, 2011	Group: Non-polymer description
Revision 1.3	Oct 13, 2021	Group: Database references / Derived calculations Category: database_2 / struct_conn ...database_2 / struct_conn / struct_ref_seq_dif / struct_site Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession ..._database_2.pdbx_DOI / _database_2.pdbx_database_accession / _struct_conn.pdbx_leaving_atom_flag / _struct_conn.ptnr1_auth_comp_id / _struct_conn.ptnr1_auth_seq_id / _struct_conn.ptnr1_label_asym_id / _struct_conn.ptnr1_label_atom_id / _struct_conn.ptnr1_label_comp_id / _struct_conn.ptnr1_label_seq_id / _struct_conn.ptnr2_auth_comp_id / _struct_conn.ptnr2_auth_seq_id / _struct_conn.ptnr2_label_asym_id / _struct_conn.ptnr2_label_atom_id / _struct_conn.ptnr2_label_comp_id / _struct_conn.ptnr2_label_seq_id / _struct_ref_seq_dif.details / _struct_site.pdbx_auth_asym_id / _struct_site.pdbx_auth_comp_id / _struct_site.pdbx_auth_seq_id
Revision 1.4	Sep 6, 2023	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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PDBx/mmCIF format	3lj6.cif.gz	439.1 KB	Display	PDBx/mmCIF format
PDB format	pdb3lj6.ent.gz	358.9 KB	Display	PDB format
PDBx/mmJSON format	3lj6.json.gz		Tree view	PDBx/mmJSON format
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Validation report

Arichive directory	https://data.pdbj.org/pub/pdb/validation_reports/lj/3lj6 ftp://data.pdbj.org/pub/pdb/validation_reports/lj/3lj6	HTTPS FTP

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Related structure data

Related structure data	3lj7C 2wj1S 2vya 2wap C: citing same article (ref.) S: Starting model for refinement
Similar structure data	6mrg-3 6mrg-4 2uwh-5 5zre-1 2qt6-1 1smj-2 6mrg-2 5qj2-2 1smj-1 5ulj-2 Search similar-shape structures by Omokage search (details) Search similar-shape structures by Omokage search (details) 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

A: Fatty-acid amide hydrolase 1

hetero molecules

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

2

B: Fatty-acid amide hydrolase 1

hetero molecules

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

3

Idetical with deposited unit
defined by software

Unit cell

Length a, b, c (Å)	71.590, 105.320, 221.560
Angle α, β, γ (deg.)	90.00, 90.00, 90.00
Int Tables number	19
Space group name H-M	P2₁2₁2₁

#1: Protein	Fatty-acid amide hydrolase 1 / Oleamide hydrolase 1 / Anandamide amidohydrolase 1 Mass: 63111.664 Da / Num. of mol.: 2 / Fragment: deltaTM-FAAHM (UNP residues 30 to 579) Mutation: Trans-membrane deletion (1-30); L192F, F194Y, A377T, S435N, I491V, V495M Source method: isolated from a genetically manipulated source Source: (gene. exp.) Rattus norvegicus (Norway rat) / Gene: Faah, Faah1 / Plasmid: pET28a / Production host: Escherichia coli (E. coli) / Strain (production host): BL21 References: UniProt: P97612, Hydrolases; Acting on carbon-nitrogen bonds, other than peptide bonds; In linear amides
#2: Chemical	ChemComp-PIX / 4-(3-{[5-(trifluoromethyl)pyridin-2-yl]oxy}benzyl)piperidine-1-carboxylic acid Mass: 380.361 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C₁₉H₁₉F₃N₂O₃
#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.: 670 / Source method: isolated from a natural source / Formula: H₂O

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Experiment

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

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Sample preparation

Crystal	Density Matthews: 3.31 Å³/Da / Density % sol: 62.82 %
Crystal grow	Temperature: 287 K / Method: vapor diffusion, sitting drop / pH: 5.5 Details: 30% PEG400 100 mM MES, 400 mM LiCl 100 mM NaCl, pH 5.5, VAPOR DIFFUSION, SITTING DROP, temperature 287K

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Data collection

Diffraction	Mean temperature: 100 K
Diffraction source	Source: SYNCHROTRON / Site: APS / Beamline: 23-ID-D / Wavelength: 0.97934 Å
Detector	Type: MARMOSAIC 300 mm CCD / Detector: CCD / Date: Jun 22, 2008
Radiation	Monochromator: double crystal monochromator and K-B pair of biomorph mirrors for vertical and horizontal focusing Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelength	Wavelength: 0.97934 Å / Relative weight: 1
Reflection	Resolution: 2.42→40 Å / Num. all: 64062 / Num. obs: 64062 / % possible obs: 98.8 % / Observed criterion σ(I): -3 / Redundancy: 4.3 % / B_iso Wilson estimate: 35.7 Å² / R_merge(I) obs: 0.107 / Net I/σ(I): 11.8
Reflection shell	Resolution: 2.42→2.5 Å / Redundancy: 3 % / R_merge(I) obs: 0.474 / Mean I/σ(I) obs: 2.4 / % possible all: 88.4

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Processing

Software

Name	Version	Classification
XDS	package	data scaling
PHASER		phasing
PHENIX	(phenix.refine)	refinement
XDS	package	data reduction

Refinement

Method to determine structure:

MOLECULAR REPLACEMENT
Starting model: PDB ENTRY 2WJ1

2wj1

Resolution: 2.42→39.615 Å / SU ML: 0.29 / Isotropic thermal model: isotropic / σ(F): 1.99 / Phase error: 17.8 / Stereochemistry target values: ML

	R_factor	Num. reflection	% reflection
R_free	0.1995	3254	5.08 %
R_work	0.1606	-	-
obs	0.1626	64059	98.83 %
all	-	64062	-

Solvent computation

Shrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL / B_sol: 38.476 Å² / k_sol: 0.332 e/Å³

Displacement parameters

B_iso mean: 28.9 Å²

Refinement step

Cycle: LAST / Resolution: 2.42→39.615 Å

	Protein	Nucleic acid	Ligand	Solvent	Total
Num. atoms	8363	0	53	670	9086

Refine LS restraints

Refine-ID	Type	Dev ideal	Number
X-RAY DIFFRACTION	f_bond_d	0.011	8662
X-RAY DIFFRACTION	f_angle_d	1.257	11768
X-RAY DIFFRACTION	f_dihedral_angle_d	20.528	3238
X-RAY DIFFRACTION	f_chiral_restr	0.072	1316
X-RAY DIFFRACTION	f_plane_restr	0.006	1524

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 (%)
2.42-2.4561	0.3026	112	0.2435	2019	X-RAY DIFFRACTION	76
2.4561-2.4945	0.2539	132	0.2105	2631	X-RAY DIFFRACTION	99
2.4945-2.5354	0.2573	158	0.2039	2595	X-RAY DIFFRACTION	100
2.5354-2.5791	0.2791	136	0.1818	2639	X-RAY DIFFRACTION	100
2.5791-2.626	0.2363	150	0.171	2622	X-RAY DIFFRACTION	100
2.626-2.6765	0.2443	158	0.1669	2631	X-RAY DIFFRACTION	100
2.6765-2.7311	0.2024	150	0.1675	2638	X-RAY DIFFRACTION	100
2.7311-2.7905	0.2183	133	0.1566	2637	X-RAY DIFFRACTION	100
2.7905-2.8554	0.193	146	0.1522	2656	X-RAY DIFFRACTION	100
2.8554-2.9268	0.195	138	0.1556	2642	X-RAY DIFFRACTION	100
2.9268-3.0059	0.2295	112	0.1599	2693	X-RAY DIFFRACTION	100
3.0059-3.0943	0.1854	134	0.1576	2657	X-RAY DIFFRACTION	100
3.0943-3.1941	0.2115	144	0.1554	2660	X-RAY DIFFRACTION	100
3.1941-3.3082	0.2142	145	0.1573	2643	X-RAY DIFFRACTION	100
3.3082-3.4406	0.1976	128	0.1547	2668	X-RAY DIFFRACTION	100
3.4406-3.5971	0.1818	173	0.1505	2653	X-RAY DIFFRACTION	100
3.5971-3.7866	0.1778	139	0.1447	2680	X-RAY DIFFRACTION	100
3.7866-4.0236	0.1718	130	0.147	2691	X-RAY DIFFRACTION	100
4.0236-4.334	0.1756	134	0.1441	2690	X-RAY DIFFRACTION	100
4.334-4.7694	0.166	132	0.1296	2736	X-RAY DIFFRACTION	100
4.7694-5.4581	0.1653	155	0.1411	2697	X-RAY DIFFRACTION	100
5.4581-6.8707	0.1737	147	0.1656	2754	X-RAY DIFFRACTION	100
6.8707-39.6201	0.1559	168	0.1504	2873	X-RAY DIFFRACTION	100

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	1.1869	-0.2279	1.6442	1.0475	-0.5182	1.5902	-0.0724	0.6164	0.1267	-0.2806	0.0044	0.1282	-0.0678	-0.575	0.0826	0.2931	0.0648	-0.1158	0.3882	0.0708	0.2412	-28.6334	-13.6352	4.5113
2	0.41	0.03	0.0703	0.5374	0.5543	-1.308	0.0991	0.2902	0.0859	-0.3572	-0.064	0.0071	-0.1405	0.0005	-0.0166	0.286	0.0444	-0.0401	0.4158	0.0391	0.0697	-13.8403	-18.0382	1.3803
3	6.5371	1.6219	0.1614	-2.7035	0.5981	3.4928	-0.08	0.3566	0.7692	0.1942	0.0989	0.164	-1.101	0.2214	0.0445	0.3788	-0.0109	-0.0087	0.1555	0.15	0.3293	-9.9842	-7.2112	8.1608
4	0.7336	0.0286	0.1028	0.2236	-0.2144	0.1453	0.0229	0.1823	0.0313	-0.0571	-0.0079	0.0485	-0.1069	-0.171	-0.0191	0.1284	0.047	-0.0361	0.1898	0.0206	0.0778	-19.8347	-22.1904	16.7934
5	0.4634	0.0038	0.0511	0.4537	-0.1123	0.5411	-0.0091	0.1802	-0.017	-0.1437	-0.046	-0.0006	-0.0204	-0.0103	0.0404	0.1345	0.0154	-0.0135	0.1403	-0.0121	0.0648	-5.8653	-30.733	21.092
6	0.3661	-0.081	-0.1804	0.6809	-0.1374	0.7388	-0.0204	0.0986	-0.1248	-0.0531	-0.0358	0.1674	0.1174	-0.1822	0.0597	0.0269	-0.0248	-0.0251	0.0814	-0.0541	0.0631	-19.729	-39.8004	29.5397
7	1.2969	-0.2655	0.1128	2.1957	-0.5664	-2.543	-0.0195	0.3132	0.1035	-0.3261	0.0777	-0.0848	-0.0488	0.2263	-0.0368	0.1473	0.0079	0.0236	0.1977	0.0007	0.0946	-0.564	-34.8699	16.9533
8	-1.3445	-0.903	0.2891	0.7067	0.3461	0.5086	0.0187	-0.3183	-0.1405	0.2251	-0.0205	-0.2378	0.1013	0.2558	0.0094	0.1402	0.0288	-0.0638	0.1271	0.0222	0.1503	18.9493	-31.1646	67.5314
9	-0.5029	0.0534	-0.0466	0.8108	-0.1529	0.4158	0.0068	-0.0154	-0.0676	-0.0155	0.0215	-0.3534	0.0102	0.1568	-0.0239	0.0611	-0.001	-0.0002	0.1417	-0.0405	0.1993	25.7805	-22.1534	55.564
10	-0.1404	-1.8282	1.8197	2.8308	0.3237	4.2393	0.0889	0.3469	-0.6277	-0.0348	0.0968	0.1249	0.3065	0.733	-0.2101	0.1715	0.0987	0.0963	0.2841	-0.0354	0.3946	23.6	-32.727	47.4771
11	0.2727	-0.3912	-0.409	0.5824	0.1392	0.7407	0.0198	-0.0349	-0.0748	0.0563	0.0385	-0.0293	0.1004	0.0046	-0.053	0.0695	-0.0005	-0.0034	0.0678	-0.0008	0.1025	8.8883	-23.0541	56.5991
12	0.4524	0.0112	-0.1317	0.1005	0.186	0.8558	0.0007	0.0493	0.1005	-0.0926	-0.0199	0.001	-0.1307	0.0287	0.0212	0.0919	-0.0125	0.0002	0.0809	0.0115	0.1193	6.4601	-12.1426	43.9185
13	0.533	0.0608	0.1051	0.7406	0.3119	0.5812	-0.0028	-0.0441	0.062	-0.007	-0.0443	0.1297	-0.0768	-0.1046	0.0449	0.0566	0.0197	0.0058	0.0528	-0.0028	0.0867	-7.636	-9.076	55.5829
14	0.3434	0.146	0.222	1.9401	-0.5241	2.3106	0.0255	0.3496	0.1053	-0.2838	0.0561	-0.3416	0.0901	0.3198	0.0039	0.1089	-0.0078	0.0453	0.1134	0.0349	0.145	10.6009	-5.983	41.111

Refinement TLS group

ID	Refine-ID	Refine TLS-ID	Selection details
1	X-RAY DIFFRACTION	1	(chain A and resid 32:72)
2	X-RAY DIFFRACTION	2	(chain A and resid 73:117)
3	X-RAY DIFFRACTION	3	(chain A and resid 118:134)
4	X-RAY DIFFRACTION	4	(chain A and resid 135:259)
5	X-RAY DIFFRACTION	5	(chain A and resid 260:354)
6	X-RAY DIFFRACTION	6	(chain A and resid 355:550)
7	X-RAY DIFFRACTION	7	(chain A and resid 551:574)
8	X-RAY DIFFRACTION	8	(chain B and resid 32:72)
9	X-RAY DIFFRACTION	9	(chain B and resid 73:117)
10	X-RAY DIFFRACTION	10	(chain B and resid 118:134)
11	X-RAY DIFFRACTION	11	(chain B and resid 135:259)
12	X-RAY DIFFRACTION	12	(chain B and resid 260:354)
13	X-RAY DIFFRACTION	13	(chain B and resid 355:550)
14	X-RAY DIFFRACTION	14	(chain B and resid 551:574)

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