[English] 日本語
Yorodumi
- PDB-4wnu: Human Cytochrome P450 2D6 Quinidine Complex -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 4wnu
TitleHuman Cytochrome P450 2D6 Quinidine Complex
ComponentsCytochrome P450 2D6
Keywordsoxidoreductase/oxidoreductase inhibitor / CYP2D6 / P450 2D6 / Cytochrome P450 / MONOOXYGENASE / oxidoreductase-oxidoreductase inhibitor complex
Function / homology
Function and homology information


negative regulation of organofluorine metabolic process / Miscellaneous substrates / isoquinoline alkaloid metabolic process / Fatty acids / coumarin metabolic process / Oxidoreductases; Acting on paired donors, with incorporation or reduction of molecular oxygen; With reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen into the other donor / CYP2E1 reactions / arachidonate metabolic process / anandamide 8,9 epoxidase activity / anandamide 11,12 epoxidase activity ...negative regulation of organofluorine metabolic process / Miscellaneous substrates / isoquinoline alkaloid metabolic process / Fatty acids / coumarin metabolic process / Oxidoreductases; Acting on paired donors, with incorporation or reduction of molecular oxygen; With reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen into the other donor / CYP2E1 reactions / arachidonate metabolic process / anandamide 8,9 epoxidase activity / anandamide 11,12 epoxidase activity / anandamide 14,15 epoxidase activity / alkaloid metabolic process / alkaloid catabolic process / Biosynthesis of maresin-like SPMs / monoterpenoid metabolic process / oxidative demethylation / Xenobiotics / oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen / retinol metabolic process / estrogen metabolic process / long-chain fatty acid biosynthetic process / Aspirin ADME / steroid metabolic process / xenobiotic catabolic process / cholesterol metabolic process / xenobiotic metabolic process / monooxygenase activity / oxidoreductase activity / iron ion binding / intracellular membrane-bounded organelle / heme binding / endoplasmic reticulum membrane / endoplasmic reticulum / mitochondrion / cytoplasm
Similarity search - Function
Cytochrome P450, E-class, group I, CYP2D-like / : / Cytochrome P450, E-class, group I / Cytochrome p450 / Cytochrome P450 / Cytochrome P450, conserved site / Cytochrome P450 cysteine heme-iron ligand signature. / Cytochrome P450 / Cytochrome P450 superfamily / Cytochrome P450 ...Cytochrome P450, E-class, group I, CYP2D-like / : / Cytochrome P450, E-class, group I / Cytochrome p450 / Cytochrome P450 / Cytochrome P450, conserved site / Cytochrome P450 cysteine heme-iron ligand signature. / Cytochrome P450 / Cytochrome P450 superfamily / Cytochrome P450 / Orthogonal Bundle / Mainly Alpha
Similarity search - Domain/homology
PROTOPORPHYRIN IX CONTAINING FE / Quinidine / Cytochrome P450 2D6
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / Resolution: 2.26 Å
AuthorsWang, A. / Stout, C.D. / Johnson, E.F.
Funding support United States, 1items
OrganizationGrant numberCountry
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)R01GM031001 United States
CitationJournal: J.Biol.Chem. / Year: 2015
Title: Contributions of Ionic Interactions and Protein Dynamics to Cytochrome P450 2D6 (CYP2D6) Substrate and Inhibitor Binding.
Authors: Wang, A. / Stout, C.D. / Zhang, Q. / Johnson, E.F.
History
DepositionOct 14, 2014Deposition site: RCSB / Processing site: RCSB
Revision 1.0Jan 14, 2015Provider: repository / Type: Initial release
Revision 1.1Jan 21, 2015Group: Database references
Revision 1.2Mar 4, 2015Group: Database references
Revision 1.3Sep 13, 2017Group: Author supporting evidence / Database references ...Author supporting evidence / Database references / Derived calculations / Other / Refinement description / Source and taxonomy
Category: citation / entity_src_gen ...citation / entity_src_gen / pdbx_audit_support / pdbx_database_status / pdbx_struct_oper_list / software
Item: _citation.journal_id_CSD / _entity_src_gen.pdbx_alt_source_flag ..._citation.journal_id_CSD / _entity_src_gen.pdbx_alt_source_flag / _pdbx_audit_support.funding_organization / _pdbx_database_status.pdb_format_compatible / _pdbx_struct_oper_list.symmetry_operation / _software.name
Revision 1.4Nov 22, 2017Group: Refinement description / Category: software / Item: _software.classification
Revision 1.5Dec 25, 2019Group: Author supporting evidence / Category: pdbx_audit_support / Item: _pdbx_audit_support.funding_organization
Revision 1.6Sep 27, 2023Group: Data collection / Database references ...Data collection / Database references / Derived calculations / Refinement description
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / database_2 / diffrn_radiation_wavelength / pdbx_initial_refinement_model / pdbx_struct_conn_angle / refine_hist / struct_conn
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession ..._database_2.pdbx_DOI / _database_2.pdbx_database_accession / _pdbx_struct_conn_angle.ptnr1_auth_asym_id / _pdbx_struct_conn_angle.ptnr1_auth_comp_id / _pdbx_struct_conn_angle.ptnr1_auth_seq_id / _pdbx_struct_conn_angle.ptnr1_label_asym_id / _pdbx_struct_conn_angle.ptnr1_label_atom_id / _pdbx_struct_conn_angle.ptnr1_label_comp_id / _pdbx_struct_conn_angle.ptnr1_label_seq_id / _pdbx_struct_conn_angle.ptnr2_auth_asym_id / _pdbx_struct_conn_angle.ptnr2_auth_comp_id / _pdbx_struct_conn_angle.ptnr2_auth_seq_id / _pdbx_struct_conn_angle.ptnr2_label_asym_id / _pdbx_struct_conn_angle.ptnr2_label_atom_id / _pdbx_struct_conn_angle.ptnr2_label_comp_id / _pdbx_struct_conn_angle.ptnr2_symmetry / _pdbx_struct_conn_angle.ptnr3_auth_asym_id / _pdbx_struct_conn_angle.ptnr3_auth_comp_id / _pdbx_struct_conn_angle.ptnr3_auth_seq_id / _pdbx_struct_conn_angle.ptnr3_label_asym_id / _pdbx_struct_conn_angle.ptnr3_label_atom_id / _pdbx_struct_conn_angle.ptnr3_label_comp_id / _pdbx_struct_conn_angle.ptnr3_label_seq_id / _pdbx_struct_conn_angle.value / _refine_hist.pdbx_number_atoms_nucleic_acid / _refine_hist.pdbx_number_atoms_protein / _struct_conn.pdbx_dist_value / _struct_conn.ptnr1_auth_asym_id / _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.ptnr1_symmetry / _struct_conn.ptnr2_auth_asym_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_conn.ptnr2_symmetry

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Cytochrome P450 2D6
B: Cytochrome P450 2D6
C: Cytochrome P450 2D6
D: Cytochrome P450 2D6
hetero molecules


Theoretical massNumber of molelcules
Total (without water)220,24631
Polymers214,9224
Non-polymers5,32427
Water12,052669
1
A: Cytochrome P450 2D6
hetero molecules


Theoretical massNumber of molelcules
Total (without water)55,24910
Polymers53,7311
Non-polymers1,5189
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
2
B: Cytochrome P450 2D6
hetero molecules


Theoretical massNumber of molelcules
Total (without water)54,9076
Polymers53,7311
Non-polymers1,1775
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
3
C: Cytochrome P450 2D6
hetero molecules


Theoretical massNumber of molelcules
Total (without water)54,9997
Polymers53,7311
Non-polymers1,2696
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
4
D: Cytochrome P450 2D6
hetero molecules


Theoretical massNumber of molelcules
Total (without water)55,0918
Polymers53,7311
Non-polymers1,3617
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Unit cell
Length a, b, c (Å)57.340, 192.114, 250.749
Angle α, β, γ (deg.)90.000, 90.000, 90.000
Int Tables number19
Space group name H-MP212121
Detailsmonomeric

-
Components

-
Protein , 1 types, 4 molecules ABCD

#1: Protein
Cytochrome P450 2D6 / CYPIID6 / Cytochrome P450-DB1 / Debrisoquine 4-hydroxylase


Mass: 53730.566 Da / Num. of mol.: 4 / Fragment: UNP RESIDUES 34-497
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: CYP2D6, CYP2DL1 / Plasmid: PCWORI / Production host: ESCHERICHIA COLI (E. coli) / Strain (production host): DH5ALPHA / References: UniProt: P10635, unspecific monooxygenase

-
Non-polymers , 6 types, 696 molecules

#2: Chemical
ChemComp-HEM / PROTOPORPHYRIN IX CONTAINING FE / HEME


Mass: 616.487 Da / Num. of mol.: 4 / Source method: obtained synthetically / Formula: C34H32FeN4O4
#3: Chemical
ChemComp-QDN / Quinidine / (9S)-6'-methoxycinchonan-9-ol


Mass: 324.417 Da / Num. of mol.: 4 / Source method: obtained synthetically / Formula: C20H24N2O2
#4: Chemical
ChemComp-DMS / DIMETHYL SULFOXIDE


Mass: 78.133 Da / Num. of mol.: 4 / Source method: obtained synthetically / Formula: C2H6OS / Comment: DMSO, precipitant*YM
#5: Chemical
ChemComp-ZN / ZINC ION


Mass: 65.409 Da / Num. of mol.: 5 / Source method: obtained synthetically / Formula: Zn
#6: Chemical
ChemComp-GOL / GLYCEROL / GLYCERIN / PROPANE-1,2,3-TRIOL


Mass: 92.094 Da / Num. of mol.: 10 / Source method: obtained synthetically / Formula: C3H8O3
#7: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 669 / Source method: isolated from a natural source / Formula: H2O

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 3.21 Å3/Da / Density % sol: 61.72 %
Crystal growTemperature: 298 K / Method: vapor diffusion, hanging drop
Details: PEG3350, SODIUM ACETATE, SODIUM CACODYLATE, POTASSIUM PHOSPHATE, SODIUM CHLORIDE, ZINC CHLORIDE, GLYCEROL, BETA-MERCAPTOETHANOL, THIORIDAZINE, HEGA-10, FACIAL AMPHIPHILE 231_CHOL. Quinidine ...Details: PEG3350, SODIUM ACETATE, SODIUM CACODYLATE, POTASSIUM PHOSPHATE, SODIUM CHLORIDE, ZINC CHLORIDE, GLYCEROL, BETA-MERCAPTOETHANOL, THIORIDAZINE, HEGA-10, FACIAL AMPHIPHILE 231_CHOL. Quinidine was added to the mother liquor after crystallization of the P450 2D6 thiordidazine complex.

-
Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: SYNCHROTRON / Site: SSRL / Beamline: BL7-1 / Wavelength: 1.097173 Å
DetectorType: ADSC QUANTUM 315r / Detector: CCD / Date: Jul 25, 2011 / Details: Rh coated flat mirror
RadiationMonochromator: Side scattering bent cube-root I-beam single crystal
Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1.097173 Å / Relative weight: 1
ReflectionResolution: 2.26→38.72 Å / Num. obs: 128917 / % possible obs: 98.7 % / Redundancy: 4.2 % / Biso Wilson estimate: 35.66 Å2 / CC1/2: 0.998 / Rmerge(I) obs: 0.056 / Rpim(I) all: 0.032 / Net I/σ(I): 17.3 / Num. measured all: 535220
Reflection shell

Diffraction-ID: 1 / Rejects: _

Resolution (Å)Redundancy (%)Rmerge(I) obsMean I/σ(I) obsNum. measured allNum. unique allCC1/2Rpim(I) all% possible all
2.26-2.34.30.39142752164180.9210.21499.8
12.38-38.723.50.0435.330818790.9960.02694.3

-
Processing

Software
NameVersionClassification
PHENIXrefinement
Aimless0.2.17data scaling
PDB_EXTRACT3.15data extraction
RefinementStarting model: 3TBG

3tbg


Resolution: 2.26→38.038 Å / SU ML: 0.24 / Cross valid method: THROUGHOUT / σ(F): 1.05 / Phase error: 24.42 / Stereochemistry target values: ML
RfactorNum. reflection% reflectionSelection details
Rfree0.2318 6489 5.04 %Random Selection
Rwork0.1897 122265 --
obs0.1918 128754 98.4 %-
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL
Displacement parametersBiso max: 145.31 Å2 / Biso mean: 49.8595 Å2 / Biso min: 17.48 Å2
Refinement stepCycle: final / Resolution: 2.26→38.038 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms14289 0 349 669 15307
Biso mean--39.22 48.65 -
Num. residues----1804
Refine LS restraints
Refine-IDTypeDev idealNumber
X-RAY DIFFRACTIONf_bond_d0.00815059
X-RAY DIFFRACTIONf_angle_d1.0520484
X-RAY DIFFRACTIONf_chiral_restr0.0392211
X-RAY DIFFRACTIONf_plane_restr0.0052702
X-RAY DIFFRACTIONf_dihedral_angle_d14.8795574
LS refinement shell

Refine-ID: X-RAY DIFFRACTION / Total num. of bins used: 30

Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkNum. reflection all% reflection obs (%)
2.26-2.28570.29281980.24641204318100
2.2857-2.31260.282270.229540254252100
2.3126-2.34080.26752010.213640664267100
2.3408-2.37040.22382340.205140684302100
2.3704-2.40160.24212240.218941044328100
2.4016-2.43450.27062090.213840534262100
2.4345-2.46930.25852350.2174056429199
2.4693-2.50610.2572350.221641044339100
2.5061-2.54530.24772140.21934002421699
2.5453-2.5870.28182110.20941264337100
2.587-2.63160.25122500.21394038428899
2.6316-2.67940.24832160.20763996421299
2.6794-2.73090.24811900.2074162435299
2.7309-2.78670.29742330.20633976420999
2.7867-2.84720.22492070.20624083429099
2.8472-2.91340.23572260.20614010423698
2.9134-2.98630.27362040.20964071427598
2.9863-3.0670.27792170.2144034425198
3.067-3.15720.25241950.2094054424998
3.1572-3.2590.26032060.19774025423197
3.259-3.37550.23932330.1994053428697
3.3755-3.51050.25242030.1963947415097
3.5105-3.67020.22532290.18764007423697
3.6702-3.86350.2322270.17924022424996
3.8635-4.10530.20832110.16964028423996
4.1053-4.42180.18252140.16084059427397
4.4218-4.8660.18242160.14454096431297
4.866-5.56820.21142060.16934181438799
5.5682-7.00820.23521960.189443154511100
7.0082-38.04330.19882220.17654384460697

+
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