PDB-4rxa: Crystal structure of human farnesyl diphosphate synthase in compl...

ID or keywords:

Entry

Database: PDB / ID: 4rxa

Title

Crystal structure of human farnesyl diphosphate synthase in complex with BPH-1358

Components

Farnesyl pyrophosphate synthase

Dimethylallyltranstransferase

Keywords

TRANSFERASE /

Prenylation

Function / homology

Function and homology information

geranyl diphosphate biosynthetic process /

dimethylallyltranstransferase / (2E,6E)-farnesyl diphosphate synthase / Cholesterol biosynthesis / farnesyl diphosphate biosynthetic process /

dimethylallyltranstransferase activity /

geranyltranstransferase activity / cholesterol biosynthetic process / Activation of gene expression by SREBF (SREBP) /

RNA binding ...
Similarity search - Function

Biological species

Homo sapiens (human)

Method

X-RAY DIFFRACTION /

SYNCHROTRON / Resolution: 2.2 Å

Authors

Liu, Y.-L. / Cao, R. / Wang, Y. / Oldfield, E.

Citation

Journal: ACS Med Chem Lett / Year: 2015
Title: Farnesyl diphosphate synthase inhibitors with unique ligand-binding geometries.
Authors: Liu, Y.L. / Cao, R. / Wang, Y. / Oldfield, E.

History

Deposition	Dec 9, 2014	Deposition site: RCSB / Processing site: RCSB
Revision 1.0	Apr 15, 2015	Provider: repository / Type: Initial release
Revision 1.1	Feb 28, 2024	Group: Data collection / Database references / Derived calculations Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / database_2 / struct_site Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession ..._database_2.pdbx_DOI / _database_2.pdbx_database_accession / _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	4rxa.cif.gz	85 KB	Display	PDBx/mmCIF format
PDB format	pdb4rxa.ent.gz	64.6 KB	Display	PDB format
PDBx/mmJSON format	4rxa.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/rx/4rxa ftp://data.pdbj.org/pub/pdb/validation_reports/rx/4rxa	HTTPS FTP

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Related structure data

Related structure data	4rxcC 4rxdC 4rxeC 4rypC C: citing same article (ref.)
Similar structure data	4lpg-1 3n5j-1 6o13-1 5dgs-1 6n7y-1 3n1v-1 5ja0-1 3n1w-1 6oag-1 6mrh-1 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
Related items in Molecule of the Month	#201 - Sep 2016 Isoprene Synthase similarity (8) #96 - Dec 2007 Oxidosqualene Cyclase similarity (1)

Deposited unit

A: Farnesyl pyrophosphate synthase

hetero molecules

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

1

A: Farnesyl pyrophosphate synthase

hetero molecules

A: Farnesyl pyrophosphate synthase

hetero molecules

defined by author&software
81.3 kDa, 2 polymers
Search similar-shape structures of this assembly by Omokage search (details)

Unit cell

Length a, b, c (Å)	110.757, 110.757, 77.960
Angle α, β, γ (deg.)	90.000, 90.000, 90.000
Int Tables number	92
Space group name H-M	P4₁2₁2

#1: Protein	Farnesyl pyrophosphate synthase / Dimethylallyltranstransferase / FPP synthase / FPS / (2E / 6E)-farnesyl diphosphate synthase / Dimethylallyltranstransferase / ...FPP synthase / FPS / (2E / 6E)-farnesyl diphosphate synthase / Dimethylallyltranstransferase / Farnesyl diphosphate synthase / Geranyltranstransferase Mass: 40029.691 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: FDPS, FPS, KIAA1293 / Production host: Escherichia coli (E. coli) References: UniProt: P14324, (2E,6E)-farnesyl diphosphate synthase, dimethylallyltranstransferase
#2: Chemical	ChemComp-3F2 / N,N'-bis[3-(4,5-dihydro-1H-imidazol-2-yl)phenyl]biphenyl-4,4'-dicarboxamide / BPH-1358 Mass: 528.604 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C₃₂H₂₈N₆O₂
#3: Chemical	ChemComp-PO4 / PHOSPHATE ION / Phosphate Mass: 94.971 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: PO₄
#4: Water	ChemComp-HOH / water / Water Mass: 18.015 Da / Num. of mol.: 104 / 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: 2.99 Å³/Da / Density % sol: 58.86 %
Crystal grow	Temperature: 293 K / Method: vapor diffusion, hanging drop / pH: 5.6 Details: 1.2M NA/K phosphate, 25% glycerol, pH 5.6, VAPOR DIFFUSION, HANGING DROP, temperature 293K

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Data collection

Diffraction	Mean temperature: 298 K
Diffraction source	Source: SYNCHROTRON / Site: APS / Beamline: 21-ID-G / Wavelength: 0.97857 Å
Detector	Type: MARMOSAIC 300 mm CCD / Detector: CCD / Date: Aug 16, 2014
Radiation	Monochromator: C(111) / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelength	Wavelength: 0.97857 Å / Relative weight: 1
Reflection	Resolution: 2.2→55.41 Å / Num. obs: 20748 / % possible obs: 100 % / Observed criterion σ(F): 1 / Observed criterion σ(I): 1
Reflection shell	Resolution: 2.2→2.4 Å / R_merge(I) obs: 0.472 / % possible all: 100

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Processing

Software

Name	Version	Classification
REFMAC	5.8.0073	refinement
PDB_EXTRACT	3.15	data extraction
HKL-3000		data collection
HKL-3000		data reduction
HKL-3000		data scaling
PHASES		phasing

Refinement

Resolution: 2.2→78.32 Å / Cor.coef. F_o:F_c: 0.939 / Cor.coef. F_o:F_c free: 0.918 / SU B: 14.561 / SU ML: 0.179 / Cross valid method: THROUGHOUT / σ(F): 0 / ESU R: 0.251 / ESU R Free: 0.212 / Stereochemistry target values: MAXIMUM LIKELIHOOD
Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS U VALUES : RESIDUAL ONLY

	R_factor	Num. reflection	% reflection	Selection details
R_free	0.2629	1152	4.9 %	RANDOM
R_work	0.2213	22572	-	-
obs	0.2234	-	94.32 %	-

Solvent computation

Ion probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å / Solvent model: MASK

Displacement parameters

B_iso max: 95.12 Å² / B_iso mean: 27.135 Å² / B_iso min: 11.12 Å²

	B_aniso -1	B_aniso -2	B_aniso -3
1-	0.85 Å²	0 Å²	0 Å²
2-	-	0.85 Å²	0 Å²
3-	-	-	-1.69 Å²

Refinement step

Cycle: LAST / Resolution: 2.2→78.32 Å

	Protein	Nucleic acid	Ligand	Solvent	Total
Num. atoms	2659	0	45	104	2808

Refine LS restraints

Refine-ID	Type	Dev ideal	Dev ideal target	Number
X-RAY DIFFRACTION	r_bond_refined_d	0.018	0.02	2761
X-RAY DIFFRACTION	r_bond_other_d	0.002	0.02	2613
X-RAY DIFFRACTION	r_angle_refined_deg	0.896	1.985	3736
X-RAY DIFFRACTION	r_angle_other_deg	0.573	3.005	5993
X-RAY DIFFRACTION	r_dihedral_angle_1_deg	6.76	5	324
X-RAY DIFFRACTION	r_dihedral_angle_2_deg	35.977	24.701	134
X-RAY DIFFRACTION	r_dihedral_angle_3_deg	17.821	15	470
X-RAY DIFFRACTION	r_dihedral_angle_4_deg	20.212	15	14
X-RAY DIFFRACTION	r_chiral_restr	0.069	0.2	405
X-RAY DIFFRACTION	r_gen_planes_refined	0.013	0.02	3105
X-RAY DIFFRACTION	r_gen_planes_other	0.002	0.02	647
X-RAY DIFFRACTION	r_mcbond_it	1.696	2.526	1314
X-RAY DIFFRACTION	r_mcbond_other	1.69	2.525	1313
X-RAY DIFFRACTION	r_mcangle_it	2.507	3.781	1632

LS refinement shell

Resolution: 2.201→2.258 Å / Total num. of bins used: 20

	R_factor	Num. reflection	% reflection
R_free	0.345	96	-
R_work	0.328	1639	-
all	-	1735	-
obs	-	-	94.91 %

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	254.29	-92.6287	68.7136	39.2047	-76.8122	512.3201	-25.7762	-10.2354	4.6658	6.3145	2.3795	-3.5705	22.1016	12.5274	23.3967	4.7705	1.1912	0.9263	3.5566	3.4202	7.7821	4.9651	36.0846	-22.3271
2	49.758	37.9985	9.2717	29.2298	8.8494	17.8144	-1.6061	1.2992	0.0621	-1.1295	1.0778	-0.0746	0.8861	1.2001	0.5283	0.3229	-0.15	0.3125	0.6774	0.4884	2.0174	-1.1118	31.6007	-27.2691
3	28.9614	11.8358	0.5802	27.5031	-0.2368	9.3834	-0.213	0.9205	-0.8047	-0.955	0.4557	-1.2506	-0.3312	0.8255	-0.2428	0.2384	-0.0929	0.0987	0.4496	0.0375	0.2801	-6.0539	26.144	-33.5636
4	27.907	8.8644	-2.9708	3.2723	-0.7124	0.4352	0.4818	0.4238	-0.2308	0.3646	-0.3026	-0.4276	0.0564	-0.2397	-0.1792	0.7645	-0.0045	0.064	0.8747	0.0397	0.6934	-13.1533	19.4831	-41.4458
5	5.3448	0.5439	3.9788	5.7763	-1.3856	3.62	-1.3419	1.1737	0.3052	-0.9129	0.9676	-0.5689	-0.902	0.7235	0.3744	0.6352	-0.5382	0.1146	0.5217	-0.0464	0.1934	-8.2796	29.9845	-25.0495
6	7.9489	1.6463	4.8164	0.3487	1.0031	2.9226	0.4876	2.6822	-1.7557	0.158	0.5807	-0.38	0.3395	1.6586	-1.0683	0.6187	0.542	0.2049	2.0674	-0.2158	1.5398	13.3547	19.8782	-19.354
7	39.0262	-14.0731	-23.4051	17.5804	5.4296	20.7808	0.4311	0.5617	1.3051	-0.2909	0.1901	-0.8904	-0.0641	1.323	-0.6212	0.2325	-0.1414	0.0303	0.7387	0.0242	0.3805	5.0703	22.3328	-25.7635
8	17.1739	-4.8658	-1.3161	3.0225	0.4617	1.8197	-0.1226	-0.5009	0.559	0.0139	0.1714	-0.1883	-0.319	0.2922	-0.0488	0.1064	-0.0294	-0.0033	0.0868	0.0114	0.1866	-14.6348	29.4386	-18.3381
9	6.77	1.5305	6.7698	18.4688	4.3816	15.144	-0.4291	0.5119	0.5574	-0.5557	0.2255	-0.3976	-1.0029	0.8017	0.2035	0.1995	-0.0362	-0.0437	0.0858	0.0317	0.3193	-21.6504	39.3935	-22.841
10	7.8995	-3.5574	2.958	5.8083	-0.6958	1.9729	0.1376	0.6772	-0.3744	-0.3388	0.017	-0.478	0.0636	0.4317	-0.1546	0.0703	-0.0039	0.045	0.131	-0.0565	0.2652	-10.5489	18.3321	-23.7076
11	18.2053	-7.9559	-11.1959	8.3363	9.7107	12.0783	-0.0001	-0.8579	0.3331	0.3692	0.0647	-0.0237	0.3358	0.0034	-0.0646	0.0633	-0.0627	-0.0076	0.264	-0.0094	0.145	-18.3404	22.9742	-8.2957
12	11.8913	-1.1723	3.1001	10.1501	6.8328	5.8892	-0.2942	0.2771	-0.3485	-1.0355	-0.1866	0.872	-0.8547	-0.0171	0.4807	0.5718	0.0676	-0.0074	0.8971	-0.0255	0.5449	-30.0585	34.9406	1.5742
13	10.6825	-3.1325	-3.4121	4.2808	2.8312	3.8784	-0.0708	-0.6568	-0.1018	0.3932	-0.0353	-0.0245	0.1937	0.1074	0.1061	0.0873	-0.0346	-0.067	0.2201	0.0152	0.2363	-9.283	24.9133	-4.9801
14	7.0289	-2.8485	2.5227	25.1433	11.7574	12.3265	0.1474	-0.4805	-0.9061	0.7781	0.1361	-0.1993	1.2167	0.0492	-0.2835	0.2257	-0.0449	-0.075	0.2791	0.0879	0.3254	-0.0393	17.1083	-2.8909
15	6.4126	-7.7432	0.4896	26.1007	0.8453	2.5431	-0.0676	0	0.7951	-0.1287	-0.0469	-0.4871	-0.3502	-0.3175	0.1145	0.2138	-0.0074	-0.0724	0.3516	-0.0288	0.3744	-9.3507	39.0189	-1.3513
16	5.5439	1.4408	1.4074	7.55	1.3511	7.3842	-0.4315	-0.0263	1.2355	-0.7016	-0.3647	0.3179	-0.6506	-0.7692	0.7962	0.2817	0.1348	-0.1133	0.5704	-0.166	0.6832	-17.6723	43.0145	-1.768
17	8.7256	-1.0463	12.2827	0.83	-1.862	17.5182	0.1596	-0.9427	0.4528	0.2491	-0.3813	0.6685	0.161	-1.017	0.2217	0.6395	0.0567	0.2053	0.9051	-0.3052	1.0316	-25.0878	43.1449	13.8463
18	1.8286	-4.2069	1.6178	9.7407	-3.755	1.4656	0.2226	0.0465	-0.26	-0.3498	0.0158	0.5139	0.132	-0.1162	-0.2384	0.6139	0.0706	-0.0556	0.8954	-0.1515	0.8366	-28.1501	47.2318	1.6444
19	15.8001	-11.7039	-0.4138	10.8178	0.9582	1.413	-0.0851	-0.7755	0.8266	0.2916	0.0974	-0.0361	-0.2694	-0.2403	-0.0124	0.3639	0.0491	-0.087	0.4246	-0.169	0.5331	-7.8651	41.8623	7.5633
20	9.6898	-2.5405	0.2318	11.281	-2.827	6.3492	0.0505	-0.1405	0.452	0.3436	0.2576	-0.4935	-0.1145	-0.1648	-0.3081	0.1058	0.0135	-0.1423	0.2253	-0.0407	0.4566	5.1886	28.8962	-2.0368

Refinement TLS group

ID	Refine-ID	Refine TLS-ID	Auth asym-ID	Auth seq-ID
1	X-RAY DIFFRACTION	1	A	12 - 16
2	X-RAY DIFFRACTION	2	A	17 - 21
3	X-RAY DIFFRACTION	3	A	22 - 29
4	X-RAY DIFFRACTION	4	A	30 - 36
5	X-RAY DIFFRACTION	5	A	37 - 70
6	X-RAY DIFFRACTION	6	A	71 - 78
7	X-RAY DIFFRACTION	7	A	79 - 86
8	X-RAY DIFFRACTION	8	A	87 - 108
9	X-RAY DIFFRACTION	9	A	109 - 124
10	X-RAY DIFFRACTION	10	A	125 - 158
11	X-RAY DIFFRACTION	11	A	159 - 178
12	X-RAY DIFFRACTION	12	A	179 - 187
13	X-RAY DIFFRACTION	13	A	188 - 219
14	X-RAY DIFFRACTION	14	A	220 - 232
15	X-RAY DIFFRACTION	15	A	233 - 251
16	X-RAY DIFFRACTION	16	A	252 - 275
17	X-RAY DIFFRACTION	17	A	276 - 285
18	X-RAY DIFFRACTION	18	A	287 - 299
19	X-RAY DIFFRACTION	19	A	301 - 327
20	X-RAY DIFFRACTION	20	A	328 - 350

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