[English] 日本語
Yorodumi
- PDB-7ufa: CYP3A4 bound to an inhibitor -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 7ufa
TitleCYP3A4 bound to an inhibitor
ComponentsCytochrome P450 3A4
KeywordsOXIDOREDUCTASE/INHIBITOR / CYP3A4 / inhibitor / complex / OXIDOREDUCTASE / OXIDOREDUCTASE-INHIBITOR complex
Function / homology
Function and homology information


quinine 3-monooxygenase / 1,8-cineole 2-exo-monooxygenase / albendazole monooxygenase (sulfoxide-forming) / quinine 3-monooxygenase activity / 1,8-cineole 2-exo-monooxygenase activity / 1-alpha,25-dihydroxyvitamin D3 23-hydroxylase activity / vitamin D3 25-hydroxylase activity / vitamin D 24-hydroxylase activity / vitamin D catabolic process / retinoic acid 4-hydroxylase activity ...quinine 3-monooxygenase / 1,8-cineole 2-exo-monooxygenase / albendazole monooxygenase (sulfoxide-forming) / quinine 3-monooxygenase activity / 1,8-cineole 2-exo-monooxygenase activity / 1-alpha,25-dihydroxyvitamin D3 23-hydroxylase activity / vitamin D3 25-hydroxylase activity / vitamin D 24-hydroxylase activity / vitamin D catabolic process / retinoic acid 4-hydroxylase activity / caffeine oxidase activity / estrogen 16-alpha-hydroxylase activity / lipid hydroxylation / aflatoxin metabolic process / anandamide 8,9 epoxidase activity / anandamide 11,12 epoxidase activity / anandamide 14,15 epoxidase activity / testosterone 6-beta-hydroxylase activity / alkaloid catabolic process / Aflatoxin activation and detoxification / Biosynthesis of maresin-like SPMs / monoterpenoid metabolic process / estrogen 2-hydroxylase activity / oxidative demethylation / vitamin D metabolic process / steroid catabolic process / Atorvastatin ADME / steroid hydroxylase activity / Xenobiotics / Phase I - Functionalization of compounds / retinoic acid metabolic process / retinol metabolic process / estrogen metabolic process / unspecific monooxygenase / long-chain fatty acid biosynthetic process / Prednisone ADME / Aspirin ADME / steroid metabolic process / androgen metabolic process / xenobiotic catabolic process / cholesterol metabolic process / steroid binding / xenobiotic metabolic process / monooxygenase activity / oxygen binding / lipid metabolic process / oxidoreductase activity / iron ion binding / intracellular membrane-bounded organelle / heme binding / endoplasmic reticulum membrane / enzyme binding / cytoplasm
Similarity search - Function
Cytochrome P450, E-class, group II / Cytochrome P450, E-class, CYP3A / : / Cytochrome P450, conserved site / Cytochrome P450 cysteine heme-iron ligand signature. / Cytochrome P450 / Cytochrome P450 superfamily / Cytochrome P450
Similarity search - Domain/homology
PROTOPORPHYRIN IX CONTAINING FE / Chem-NI6 / Cytochrome P450 3A4
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.5 Å
AuthorsSevrioukova, I.
Funding support United States, 1items
OrganizationGrant numberCountry
National Institutes of Health/National Institute of Environmental Health Sciences (NIH/NIEHS)ES025767 United States
CitationJournal: Int J Mol Sci / Year: 2022
Title: Interaction of CYP3A4 with Rationally Designed Ritonavir Analogues: Impact of Steric Constraints Imposed on the Heme-Ligating Group and the End-Pyridine Attachment.
Authors: Samuels, E.R. / Sevrioukova, I.F.
History
DepositionMar 22, 2022Deposition site: RCSB / Processing site: RCSB
Revision 1.0Jul 27, 2022Provider: repository / Type: Initial release
Revision 1.1Oct 18, 2023Group: Data collection / Refinement description
Category: chem_comp_atom / chem_comp_bond / pdbx_initial_refinement_model

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Cytochrome P450 3A4
hetero molecules


Theoretical massNumber of molelcules
Total (without water)56,9083
Polymers55,7581
Non-polymers1,1502
Water1086
1
A: Cytochrome P450 3A4
hetero molecules

A: Cytochrome P450 3A4
hetero molecules


Theoretical massNumber of molelcules
Total (without water)113,8166
Polymers111,5162
Non-polymers2,3004
Water362
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
crystal symmetry operation4_555x,-y,-z1
Unit cell
Length a, b, c (Å)76.580, 101.730, 125.510
Angle α, β, γ (deg.)90.00, 90.00, 90.00
Int Tables number23
Space group name H-MI222

-
Components

#1: Protein Cytochrome P450 3A4 / 1 / 4-cineole 2-exo-monooxygenase / 8-cineole 2-exo-monooxygenase / Albendazole monooxygenase ...1 / 4-cineole 2-exo-monooxygenase / 8-cineole 2-exo-monooxygenase / Albendazole monooxygenase (sulfoxide-forming) / Albendazole sulfoxidase / CYPIIIA3 / CYPIIIA4 / Cholesterol 25-hydroxylase / Cytochrome P450 3A3 / Cytochrome P450 HLp / Cytochrome P450 NF-25 / Cytochrome P450-PCN1 / Nifedipine oxidase / Quinine 3-monooxygenase


Mass: 55757.812 Da / Num. of mol.: 1 / Mutation: residues 3-22 deleted, C-terminal 4-histidine tag
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: CYP3A4, CYP3A3 / Production host: Escherichia coli BL21(DE3) (bacteria) / Variant (production host): C41
References: UniProt: P08684, unspecific monooxygenase, 1,8-cineole 2-exo-monooxygenase, albendazole monooxygenase (sulfoxide-forming), quinine 3-monooxygenase
#2: Chemical ChemComp-HEM / PROTOPORPHYRIN IX CONTAINING FE / HEME


Mass: 616.487 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Formula: C34H32FeN4O4
#3: Chemical ChemComp-NI6 / tert-butyl [(2S)-1-{[(2R)-1-oxo-3-phenyl-1-{[3-(pyridin-4-yl)propyl]amino}propan-2-yl]sulfanyl}-3-phenylpropan-2-yl]carbamate


Mass: 533.725 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C31H39N3O3S / Feature type: SUBJECT OF INVESTIGATION
#4: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 6 / Source method: isolated from a natural source / Formula: H2O
Has ligand of interestY

-
Experimental details

-
Experiment

ExperimentMethod: X-RAY DIFFRACTION / Number of used crystals: 1

-
Sample preparation

CrystalDensity Matthews: 2.19 Å3/Da / Density % sol: 43.89 %
Crystal growTemperature: 298 K / Method: microbatch / Details: PEG 3350, sodium malate pH 7.0

-
Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: ALS / Beamline: 8.2.1 / Wavelength: 1 Å
DetectorType: DECTRIS PILATUS 300K / Detector: PIXEL / Date: Mar 13, 2020 / Details: mirrors
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1 Å / Relative weight: 1
ReflectionResolution: 2.5→50.86 Å / Num. obs: 17305 / % possible obs: 99.8 % / Redundancy: 7.2 % / Biso Wilson estimate: 79 Å2 / CC1/2: 0.998 / Rmerge(I) obs: 0.089 / Rpim(I) all: 0.036 / Net I/σ(I): 9.8
Reflection shellResolution: 2.5→2.64 Å / Rmerge(I) obs: 2.524 / Mean I/σ(I) obs: 1 / Num. unique obs: 2503 / CC1/2: 0.403 / Rpim(I) all: 1.006 / % possible all: 100

-
Processing

Software
NameVersionClassification
PHENIX1.11.1_2575refinement
iMOSFLMdata reduction
SCALAdata scaling
PHASERphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 5vcc

5vcc


Resolution: 2.5→40.144 Å / SU ML: 0.5 / Cross valid method: THROUGHOUT / σ(F): 1.33 / Phase error: 33.4 / Stereochemistry target values: ML
RfactorNum. reflection% reflection
Rfree0.2835 873 5.07 %
Rwork0.247 --
obs0.2487 17212 99.22 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL
Refinement stepCycle: LAST / Resolution: 2.5→40.144 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms3609 0 81 6 3696
Refine LS restraints
Refine-IDTypeDev idealNumber
X-RAY DIFFRACTIONf_bond_d0.0033837
X-RAY DIFFRACTIONf_angle_d0.5585202
X-RAY DIFFRACTIONf_dihedral_angle_d12.332320
X-RAY DIFFRACTIONf_chiral_restr0.039572
X-RAY DIFFRACTIONf_plane_restr0.004653
LS refinement shell
Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkRefine-ID% reflection obs (%)
2.5001-2.65670.41461470.36852673X-RAY DIFFRACTION99
2.6567-2.86180.33641620.34142670X-RAY DIFFRACTION99
2.8618-3.14970.31371430.31762694X-RAY DIFFRACTION99
3.1497-3.60520.34891520.29272711X-RAY DIFFRACTION99
3.6052-4.54110.25731280.24372749X-RAY DIFFRACTION99
4.5411-40.1440.25191410.20542842X-RAY DIFFRACTION99
Refinement TLS params.Method: refined / Origin x: -19.0101 Å / Origin y: -23.6515 Å / Origin z: -12.7322 Å
111213212223313233
T0.4618 Å2-0.0228 Å20.0226 Å2-0.6991 Å2-0.0893 Å2--0.5655 Å2
L3.4649 °2-2.5486 °2-1.1312 °2-7.9935 °21.2445 °2--2.9995 °2
S-0.1396 Å °0.2268 Å °-0.2898 Å °0.5104 Å °0.0458 Å °-0.2488 Å °0.3749 Å °-0.0459 Å °0.0505 Å °
Refinement TLS groupSelection details: all

+
About Yorodumi

-
News

-
Feb 9, 2022. New format data for meta-information of EMDB entries

New format data for meta-information of EMDB entries

  • Version 3 of the EMDB header file is now the official format.
  • The previous official version 1.9 will be removed from the archive.

Related info.:EMDB header

External links:wwPDB to switch to version 3 of the EMDB data model

-
Aug 12, 2020. Covid-19 info

Covid-19 info

URL: https://pdbj.org/emnavi/covid19.php

New page: Covid-19 featured information page in EM Navigator.

Related info.:Covid-19 info / Mar 5, 2020. Novel coronavirus structure data

+
Mar 5, 2020. Novel coronavirus structure data

Novel coronavirus structure data

Related info.:Yorodumi Speices / Aug 12, 2020. Covid-19 info

External links:COVID-19 featured content - PDBj / Molecule of the Month (242)：Coronavirus Proteases

+
Jan 31, 2019. EMDB accession codes are about to change! (news from PDBe EMDB page)

EMDB accession codes are about to change! (news from PDBe EMDB page)

  • The allocation of 4 digits for EMDB accession codes will soon come to an end. Whilst these codes will remain in use, new EMDB accession codes will include an additional digit and will expand incrementally as the available range of codes is exhausted. The current 4-digit format prefixed with “EMD-” (i.e. EMD-XXXX) will advance to a 5-digit format (i.e. EMD-XXXXX), and so on. It is currently estimated that the 4-digit codes will be depleted around Spring 2019, at which point the 5-digit format will come into force.
  • The EM Navigator/Yorodumi systems omit the EMD- prefix.

Related info.:Q: What is EMD? / ID/Accession-code notation in Yorodumi/EM Navigator

External links:EMDB Accession Codes are Changing Soon! / Contact to PDBj

+
Jul 12, 2017. Major update of PDB

Major update of PDB

  • wwPDB released updated PDB data conforming to the new PDBx/mmCIF dictionary.
  • This is a major update changing the version number from 4 to 5, and with Remediation, in which all the entries are updated.
  • In this update, many items about electron microscopy experimental information are reorganized (e.g. em_software).
  • Now, EM Navigator and Yorodumi are based on the updated data.

External links:wwPDB Remediation / Enriched Model Files Conforming to OneDep Data Standards Now Available in the PDB FTP Archive

-
Yorodumi

Thousand views of thousand structures

  • Yorodumi is a browser for structure data from EMDB, PDB, SASBDB, etc.
  • This page is also the successor to EM Navigator detail page, and also detail information page/front-end page for Omokage search.
  • The word "yorodu" (or yorozu) is an old Japanese word meaning "ten thousand". "mi" (miru) is to see.

Related info.:EMDB / PDB / SASBDB / Comparison of 3 databanks / Yorodumi Search / Aug 31, 2016. New EM Navigator & Yorodumi / Yorodumi Papers / Jmol/JSmol / Function and homology information / Changes in new EM Navigator and Yorodumi

Read more