PDB-8sg5: Cytochrome P450 (CYP) 3A5 crystallized with clotrimazole

ID or keywords:

Entry

Database: PDB / ID: 8sg5

Title

Cytochrome P450 (CYP) 3A5 crystallized with clotrimazole

Components

Cytochrome P450 3A5

Keywords

OXIDOREDUCTASE / Inhibitor /

complex / CYP /

cytochrome P450

Function / homology

Function and homology information

testosterone 6-beta-hydroxylase activity / retinoic acid 4-hydroxylase activity / aflatoxin metabolic process / estrogen 16-alpha-hydroxylase activity / lipid hydroxylation / alkaloid catabolic process / Aflatoxin activation and detoxification /

Xenobiotics / oxidative demethylation / estrogen metabolic process ...
Similarity search - Function

Biological species

Homo sapiens (human)

Method

X-RAY DIFFRACTION /

SYNCHROTRON /

MOLECULAR REPLACEMENT / Resolution: 2.8 Å

Authors

Hsu, M.H. / Johnson, E.F.

Funding support

United States, 1items

Citation

Journal: Drug Metab.Dispos. / Year: 2023
Title: Differential Effects of Clotrimazole on X-Ray Crystal Structures of Human Cytochromes P450 3A5 and 3A4.
Authors: Hsu, M.H. / Johnson, E.F.

History

Deposition	Apr 11, 2023	Deposition site: RCSB / Processing site: RCSB
Revision 1.0	Oct 11, 2023	Provider: repository / Type: Initial release
Revision 1.1	Nov 22, 2023	Group: Database references / Category: citation Item: _citation.journal_volume / _citation.page_first ..._citation.journal_volume / _citation.page_first / _citation.page_last / _citation.title

Structure viewer	Molecule: MolmilJmol/JSmol

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Download

PDBx/mmCIF format	8sg5.cif.gz	1.7 MB	Display	PDBx/mmCIF format
PDB format	pdb8sg5.ent.gz	1.2 MB	Display	PDB format
PDBx/mmJSON format	8sg5.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/sg/8sg5 ftp://data.pdbj.org/pub/pdb/validation_reports/sg/8sg5	HTTPS FTP

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Related structure data

Related structure data	8spdC C: citing same article (ref.)
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	#82 - Oct 2006 Cytochrome p450 similarity (6) #228 - Dec 2018 Directed Evolution of Enzymes similarity (1)

Deposited unit

A: Cytochrome P450 3A5

B: Cytochrome P450 3A5

C: Cytochrome P450 3A5

D: Cytochrome P450 3A5

E: Cytochrome P450 3A5

F: Cytochrome P450 3A5

G: Cytochrome P450 3A5

H: Cytochrome P450 3A5

hetero molecules

456 kDa, 8 polymers
Search similar-shape structures of this assembly by Omokage search (details)

1

A: Cytochrome P450 3A5

hetero molecules

defined by author&software
Evidence: assay for oligomerization
57.1 kDa, 1 polymers
Search similar-shape structures of this assembly by Omokage search (details)

2

B: Cytochrome P450 3A5

hetero molecules

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

3

C: Cytochrome P450 3A5

hetero molecules

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

4

D: Cytochrome P450 3A5

hetero molecules

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

5

E: Cytochrome P450 3A5

hetero molecules

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

6

F: Cytochrome P450 3A5

hetero molecules

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

7

G: Cytochrome P450 3A5

hetero molecules

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

8

H: Cytochrome P450 3A5

hetero molecules

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

Unit cell

Length a, b, c (Å)	104.131, 200.679, 110.819
Angle α, β, γ (deg.)	90.000, 92.010, 90.000
Int Tables number	4
Space group name H-M	P12₁1
Space group name Hall	P2yb
Symmetry operation	#1: x,y,z #2: -x,y+1/2,-z

#1: Protein	Cytochrome P450 3A5 / CYPIIIA5 / Cytochrome P450 HLp2 / Cytochrome P450-PCN3 Mass: 54862.586 Da / Num. of mol.: 8 / Fragment: UNP 24-497 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: CYP3A5 / Plasmid: PCWORI / Production host: Escherichia coli (E. coli) / Strain (production host): DH-5A / References: UniProt: P20815, unspecific monooxygenase
#2: Chemical	ChemComp-HEM / PROTOPORPHYRIN IX CONTAINING FE / HEME / Heme B Mass: 616.487 Da / Num. of mol.: 8 / Source method: obtained synthetically / Formula: C₃₄H₃₂FeN₄O₄ / Feature type: SUBJECT OF INVESTIGATION
#3: Chemical	... ChemComp-CL6 / 1-[(2-CHLOROPHENYL)(DIPHENYL)METHYL]-1H-IMIDAZOLE / CLOTRIMAZOLE / Clotrimazole Mass: 344.837 Da / Num. of mol.: 24 / Source method: obtained synthetically / Formula: C₂₂H₁₇ClN₂ / Feature type: SUBJECT OF INVESTIGATION / Comment: medication, antifungal*YM
#4: Chemical	ChemComp-CE9 / DODECYL NONA ETHYLENE GLYCOL ETHER / POLYDOCANOL / THESIT / Polidocanol Mass: 582.807 Da / Num. of mol.: 7 / Source method: obtained synthetically / Formula: C₃₀H₆₂O₁₀
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: 2.64 Å³/Da / Density % sol: 53.35 %
Crystal grow	Temperature: 296 K / Method: vapor diffusion, sitting drop / pH: 7.4 / Details: C12E9, PEG 3350, sodium malonate, lithium sulfate

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Data collection

Diffraction	Mean temperature: 100 K / Serial crystal experiment: N
Diffraction source	Source: SYNCHROTRON / Site: SSRL / Beamline: BL12-1 / Wavelength: 0.97946 Å
Detector	Type: DECTRIS EIGER X 16M / Detector: PIXEL / Date: Jul 8, 2020
Radiation	Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelength	Wavelength: 0.97946 Å / Relative weight: 1
Reflection	Resolution: 2.8→39.1 Å / Num. obs: 110709 / % possible obs: 99.3 % / Redundancy: 3.8 % / B_iso Wilson estimate: 75.21 Å² / CC_1/2: 0.968 / Net I/σ(I): 6.3
Reflection shell	Resolution: 2.8→2.85 Å / Redundancy: 3.6 % / Num. unique obs: 5401 / CC_1/2: 0.492 / % possible all: 97.6

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Processing

Software

Name	Version	Classification
PHENIX	1.20.1_4487	refinement
XDS		data reduction
Aimless		data scaling
PHASER		phasing

Refinement

Method to determine structure:

MOLECULAR REPLACEMENT / Resolution: 2.8→39.1 Å / SU ML: 0.4255 / Cross valid method: THROUGHOUT / σ(F): 1.35 / Phase error: 28.472
Stereochemistry target values: GeoStd + Monomer Library + CDL v1.2

	R_factor	Num. reflection	% reflection
R_free	0.241	5599	5.06 %
R_work	0.203	104955	-
obs	0.205	110554	99.11 %

Solvent computation

Shrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL

Displacement parameters

B_iso mean: 87.4 Å²

Refinement step

Cycle: LAST / Resolution: 2.8→39.1 Å

	Protein	Nucleic acid	Ligand	Solvent	Total
Num. atoms	28951	0	1147	0	30098

Refine LS restraints

Refine-ID	Type	Dev ideal	Number
X-RAY DIFFRACTION	f_bond_d	0.003	30915
X-RAY DIFFRACTION	f_angle_d	0.5876	41932
X-RAY DIFFRACTION	f_chiral_restr	0.0413	4555
X-RAY DIFFRACTION	f_plane_restr	0.0039	5803
X-RAY DIFFRACTION	f_dihedral_angle_d	10.1795	12244

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 (%)
2.8-2.83	0.4188	161	0.3604	3419	X-RAY DIFFRACTION	95.85
2.83-2.87	0.3765	170	0.3267	3514	X-RAY DIFFRACTION	99.33
2.87-2.9	0.3269	186	0.3139	3507	X-RAY DIFFRACTION	99.6
2.9-2.94	0.3598	209	0.3115	3476	X-RAY DIFFRACTION	99.7
2.94-2.98	0.3593	190	0.3087	3561	X-RAY DIFFRACTION	99.6
2.98-3.02	0.3349	184	0.295	3455	X-RAY DIFFRACTION	99.7
3.02-3.06	0.3407	191	0.3009	3512	X-RAY DIFFRACTION	99.6
3.06-3.1	0.3419	187	0.2851	3488	X-RAY DIFFRACTION	99.57
3.1-3.15	0.314	206	0.2875	3499	X-RAY DIFFRACTION	99.46
3.15-3.21	0.3481	173	0.2901	3452	X-RAY DIFFRACTION	99.42
3.21-3.26	0.3201	161	0.2722	3575	X-RAY DIFFRACTION	99.2
3.26-3.32	0.2998	185	0.2498	3491	X-RAY DIFFRACTION	99.16
3.32-3.38	0.2997	190	0.2385	3464	X-RAY DIFFRACTION	99.21
3.38-3.45	0.2598	168	0.2429	3524	X-RAY DIFFRACTION	99.06
3.45-3.53	0.2864	212	0.2335	3450	X-RAY DIFFRACTION	98.41
3.53-3.61	0.2907	162	0.2331	3456	X-RAY DIFFRACTION	98.13
3.61-3.7	0.2664	186	0.2326	3470	X-RAY DIFFRACTION	97.91
3.7-3.8	0.2436	170	0.2158	3530	X-RAY DIFFRACTION	99.89
3.8-3.91	0.2393	165	0.1969	3508	X-RAY DIFFRACTION	99.67
3.91-4.04	0.2249	178	0.183	3575	X-RAY DIFFRACTION	99.84
4.04-4.18	0.2176	193	0.1827	3518	X-RAY DIFFRACTION	99.73
4.18-4.35	0.2489	178	0.1799	3506	X-RAY DIFFRACTION	99.7
4.35-4.55	0.1991	180	0.167	3546	X-RAY DIFFRACTION	99.65
4.55-4.79	0.2058	223	0.156	3455	X-RAY DIFFRACTION	99.32
4.79-5.08	0.2036	193	0.1651	3483	X-RAY DIFFRACTION	99
5.08-5.48	0.2238	141	0.1662	3499	X-RAY DIFFRACTION	97.25
5.48-6.03	0.2281	198	0.184	3519	X-RAY DIFFRACTION	99.76
6.03-6.89	0.2333	198	0.183	3541	X-RAY DIFFRACTION	99.65
6.89-8.67	0.1863	229	0.1669	3500	X-RAY DIFFRACTION	99.68
8.67-39.1	0.1877	232	0.1631	3462	X-RAY DIFFRACTION	97.47

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	1.24737535561	0.310207799677	0.17877124719	2.7280011887	-0.10375803156	1.66391749439	0.0349294237275	-0.13894950843	-0.0730422177467	0.251763302729	-0.0557170818283	0.102260040224	0.143271487037	-0.0317489893342	-1.84324721592	0.368390888201	0.0113772529277	0.102375655856	0.553044680695	0.0434457932899	0.503074310909	44.038	-21.632	8.72
2	1.37649599323	-0.248998273383	0.4696699923	2.0961087566	0.238698295195	2.35811433939	-0.0547166306214	0.120925311474	-0.143755545082	-0.0766051984675	0.0447442017412	-0.017379591764	0.0553992595355	0.370907158515	0.00582779400619	0.200913522179	0.0217222325215	0.103470840755	0.587931988614	-0.088685900909	0.415492006309	-1.169	-20.016	13.15
3	1.17905366743	0.141648246577	0.135224089664	1.61860657651	-0.0502825373448	1.17831410931	0.0657639935219	0.00186079522028	-0.153194422071	0.394409539026	-0.049819296569	-0.0910961458395	0.0769128772905	0.0358325577029	-1.84780493283	0.682890405169	0.00781139612318	-0.0495671407986	0.480268472144	-0.0748211275813	0.4395043333	-10.688	-16.928	64.55
4	2.02816542794	-0.420098395728	0.317907739491	1.72976594723	0.000801735733657	1.26401034892	0.0326172385507	0.0114541593786	0.406848141962	-0.06630709379	-0.0169863839167	-0.0970025698506	0.00381859689692	-0.0918382872479	0.0001383784236	0.323075995647	0.0578274041417	0.0947516565412	0.446275308656	0.0266915982258	0.499690443217	26.099	-78.331	14.179
5	0.94938688095	-0.0941342511113	0.613029646994	1.12307879785	0.160822544061	2.14714851969	-0.261872582388	0.20925338568	0.105288203079	0.0150622015197	0.113774250708	-0.0302213860952	-0.306102083447	0.156898828101	-0.0129352958325	0.550996602749	-0.0705740722204	-0.0851497671646	0.548561352954	0.0547759414283	0.677957777996	-29.506	-73.839	22.092
6	1.33273923594	0.315446885109	0.44004905714	1.59841002381	-0.503811690353	1.27325102001	-0.0880263109198	0.0613303206828	0.213303182755	-0.0780600203537	-0.0995480040314	-0.19426140698	-0.168841826072	0.0926699361131	-2.36840642964	0.676134829663	-0.0723826110686	-0.0374635223732	0.579821672968	0.0886267719218	0.585904100037	32.547	-77.179	76.878
7	1.94573821723	0.0786722465755	0.862294240669	0.882237278483	0.0599914598087	1.86825239772	-0.155502892922	-0.464952733144	0.101193594704	0.115886074674	0.00175798002245	0.0163147664833	-0.351444150399	-0.0980293060003	-0.0159288560262	0.557179416513	0.0336740250714	-0.0757365202422	0.609256185564	-0.0753835177235	0.559535975165	-19.269	-73.225	68.051
8	1.52521667392	-0.208850526799	0.478698837964	1.19305796884	-0.0476524590069	1.56746079215	0.30510708973	0.293277890457	-0.27641757668	-0.520037397414	-0.149227833906	0.0544419622897	0.74393152655	0.299636766718	0.108709170284	1.12805167247	0.161426075751	-0.0752959504161	0.597673527975	-0.0512258631521	0.526559905242	47.731	-20.639	68.885

Refinement TLS group

ID	Refine-ID	Refine TLS-ID	Selection details	Auth asym-ID	Auth seq-ID
1	X-RAY DIFFRACTION	1	( CHAIN A AND ( RESID 23:496 OR RESID 601:605 ) )	A	23 - 496
2	X-RAY DIFFRACTION	1	( CHAIN A AND ( RESID 23:496 OR RESID 601:605 ) )	A	601 - 605
3	X-RAY DIFFRACTION	2	( CHAIN B AND ( RESID 23:496 OR RESID 601:605 ) )	B	23 - 496
4	X-RAY DIFFRACTION	2	( CHAIN B AND ( RESID 23:496 OR RESID 601:605 ) )	B	601 - 605
5	X-RAY DIFFRACTION	3	( CHAIN C AND ( RESID 27:495 OR RESID 601:605 ) )	C	27 - 495
6	X-RAY DIFFRACTION	3	( CHAIN C AND ( RESID 27:495 OR RESID 601:605 ) )	C	601 - 605
7	X-RAY DIFFRACTION	4	( CHAIN D AND ( RESID 26:496 OR RESID 601:605 ) )	D	26 - 496
8	X-RAY DIFFRACTION	4	( CHAIN D AND ( RESID 26:496 OR RESID 601:605 ) )	D	601 - 605
9	X-RAY DIFFRACTION	5	( CHAIN E AND ( RESID 27:496 OR RESID 601:605 ) )	E	27 - 496
10	X-RAY DIFFRACTION	5	( CHAIN E AND ( RESID 27:496 OR RESID 601:605 ) )	E	601 - 605
11	X-RAY DIFFRACTION	6	( CHAIN F AND ( RESID 27:496 OR RESID 601:605 ) )	F	27 - 496
12	X-RAY DIFFRACTION	6	( CHAIN F AND ( RESID 27:496 OR RESID 601:605 ) )	F	601 - 605
13	X-RAY DIFFRACTION	7	( CHAIN G AND ( RESID 30:496 OR RESID 601:605 ) )	G	30 - 496
14	X-RAY DIFFRACTION	7	( CHAIN G AND ( RESID 30:496 OR RESID 601:605 ) )	G	601 - 605
15	X-RAY DIFFRACTION	8	( CHAIN H AND ( RESID 26:496 OR RESID 601:604 ) )	H	26 - 496
16	X-RAY DIFFRACTION	8	( CHAIN H AND ( RESID 26:496 OR RESID 601:604 ) )	H	601 - 604

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