[English] 日本語
Yorodumi
- PDB-8vz7: Crystal Structure of Human Cytochrome P450 2C9*27 (R150L) Genetic... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 8vz7
TitleCrystal Structure of Human Cytochrome P450 2C9*27 (R150L) Genetic Variant in Complex with the Drug Losartan
ComponentsCytochrome P450 2C9
KeywordsOXIDOREDUCTASE / Cytochrome P450 2C9*27 genetic variant
Function / homology
Function and homology information


arachidonate 14,15-epoxygenase activity / arachidonate 11,12-epoxygenase activity / amide metabolic process / (S)-limonene 6-monooxygenase / (S)-limonene 7-monooxygenase / (R)-limonene 6-monooxygenase / (S)-limonene 6-monooxygenase activity / (S)-limonene 7-monooxygenase activity / (R)-limonene 6-monooxygenase activity / urea metabolic process ...arachidonate 14,15-epoxygenase activity / arachidonate 11,12-epoxygenase activity / amide metabolic process / (S)-limonene 6-monooxygenase / (S)-limonene 7-monooxygenase / (R)-limonene 6-monooxygenase / (S)-limonene 6-monooxygenase activity / (S)-limonene 7-monooxygenase activity / (R)-limonene 6-monooxygenase activity / urea metabolic process / omega-hydroxylase P450 pathway / Synthesis of (16-20)-hydroxyeicosatetraenoic acids (HETE) / organic acid metabolic process / CYP2E1 reactions / arachidonate epoxygenase activity / icosanoid biosynthetic process / monocarboxylic acid metabolic process / epoxygenase P450 pathway / caffeine oxidase activity / Synthesis of epoxy (EET) and dihydroxyeicosatrienoic acids (DHET) / Biosynthesis of maresin-like SPMs / monoterpenoid metabolic process / estrogen 2-hydroxylase activity / oxidative demethylation / steroid hydroxylase activity / 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 / long-chain fatty acid biosynthetic process / estrogen metabolic process / unspecific monooxygenase / Aspirin ADME / steroid metabolic process / xenobiotic catabolic process / xenobiotic metabolic process / cholesterol metabolic process / monooxygenase activity / oxidoreductase activity / iron ion binding / intracellular membrane-bounded organelle / heme binding / endoplasmic reticulum membrane / plasma membrane / cytoplasm
Similarity search - Function
: / Cytochrome P450, E-class, group I / Cytochrome P450, conserved site / Cytochrome P450 cysteine heme-iron ligand signature. / Cytochrome P450 / Cytochrome P450 superfamily / Cytochrome P450
Similarity search - Domain/homology
beta-D-fructofuranose / PROTOPORPHYRIN IX CONTAINING FE / : / Chem-LSN / Cytochrome P450 2C9
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.53 Å
AuthorsShah, M.B.
Funding support1items
OrganizationGrant numberCountry
Not funded
CitationJournal: J.Inorg.Biochem. / Year: 2024
Title: Structural and biophysical analysis of cytochrome P450 2C9*14 and *27 variants in complex with losartan.
Authors: Parikh, S.J. / Edara, S. / Deodhar, S. / Singh, A.K. / Maekawa, K. / Zhang, Q. / Glass, K.C. / Shah, M.B.
History
DepositionFeb 11, 2024Deposition site: RCSB / Processing site: RCSB
Revision 1.0Jun 12, 2024Provider: repository / Type: Initial release
Revision 1.1Jun 26, 2024Group: Database references / Category: citation
Item: _citation.journal_volume / _citation.page_first ..._citation.journal_volume / _citation.page_first / _citation.page_last / _citation.pdbx_database_id_PubMed / _citation.title

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Cytochrome P450 2C9
hetero molecules


Theoretical massNumber of molelcules
Total (without water)55,8736
Polymers54,1921
Non-polymers1,6825
Water3,081171
1


  • Idetical with deposited unit
  • defined by author&software
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
Unit cell
Length a, b, c (Å)74.890, 142.170, 163.070
Angle α, β, γ (deg.)90.00, 90.00, 90.00
Int Tables number23
Space group name H-MI222

-
Components

-
Protein / Sugars , 2 types, 2 molecules A

#1: Protein Cytochrome P450 2C9 / (R)-limonene 6-monooxygenase / (S)-limonene 6-monooxygenase / (S)-limonene 7-monooxygenase / ...(R)-limonene 6-monooxygenase / (S)-limonene 6-monooxygenase / (S)-limonene 7-monooxygenase / CYPIIC9 / Cholesterol 25-hydroxylase / Cytochrome P-450MP / Cytochrome P450 MP-4 / Cytochrome P450 MP-8 / Cytochrome P450 PB-1 / S-mephenytoin 4-hydroxylase


Mass: 54191.777 Da / Num. of mol.: 1 / Mutation: R150L, V490I
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: CYP2C9, CYP2C10 / Production host: Escherichia coli (E. coli) / Strain (production host): Rosetta 2
References: UniProt: P11712, unspecific monooxygenase, (R)-limonene 6-monooxygenase, (S)-limonene 6-monooxygenase, (S)-limonene 7-monooxygenase
#4: Sugar ChemComp-FRU / beta-D-fructofuranose / beta-D-fructose / D-fructose / fructose


Type: D-saccharide, beta linking / Mass: 180.156 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C6H12O6
IdentifierTypeProgram
DFrufbCONDENSED IUPAC CARBOHYDRATE SYMBOLGMML 1.0
b-D-fructofuranoseCOMMON NAMEGMML 1.0
b-D-FrufIUPAC CARBOHYDRATE SYMBOLPDB-CARE 1.0
FruSNFG CARBOHYDRATE SYMBOLGMML 1.0

-
Non-polymers , 4 types, 175 molecules

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


Mass: 616.487 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C34H32FeN4O4
#3: Chemical ChemComp-LSN / [2-butyl-5-chloranyl-3-[[4-[2-(2H-1,2,3,4-tetrazol-5-yl)phenyl]phenyl]methyl]imidazol-4-yl]methanol / Losartan


Mass: 422.911 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C22H23ClN6O / Feature type: SUBJECT OF INVESTIGATION / Comment: medication*YM
#5: Chemical ChemComp-K / POTASSIUM ION


Mass: 39.098 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: K
#6: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 171 / Source method: isolated from a natural source / Formula: H2O

-
Details

Has ligand of interestY

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 4 Å3/Da / Density % sol: 69.29 %
Crystal growTemperature: 291 K / Method: vapor diffusion, sitting drop / pH: 7.5
Details: 0.3M Sodium Acetate Trihydrate 0.1 M Tris pH 7.5 25% w/v PEG 2000 MME
PH range: 7.4-7.5

-
Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: SSRL / Beamline: BL12-2 / Wavelength: 0.97 Å
DetectorType: DECTRIS EIGER2 S 16M / Detector: PIXEL / Date: May 29, 2021
RadiationMonochromator: Liquid nitrogen-cooled double crystal Si(111)
Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.97 Å / Relative weight: 1
ReflectionResolution: 2.53→50.01 Å / Num. obs: 29365 / % possible obs: 99.8 % / Redundancy: 5.8 % / CC1/2: 0.996 / Rpim(I) all: 0.038 / Net I/σ(I): 12.8
Reflection shellResolution: 2.53→2.6 Å / Mean I/σ(I) obs: 5.2 / Num. unique obs: 2072 / CC1/2: 0.95 / Rpim(I) all: 0.121 / % possible all: 99.9

-
Processing

Software
NameVersionClassification
REFMAC5.8.0135refinement
SCALAdata scaling
iMOSFLMdata reduction
BALBESphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT / Resolution: 2.53→50.01 Å / Cor.coef. Fo:Fc: 0.971 / Cor.coef. Fo:Fc free: 0.941 / SU B: 6.848 / SU ML: 0.149 / Cross valid method: THROUGHOUT / ESU R: 0.242 / ESU R Free: 0.216 / Stereochemistry target values: MAXIMUM LIKELIHOOD / Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS
RfactorNum. reflection% reflectionSelection details
Rfree0.21531 1494 5.1 %RANDOM
Rwork0.15092 ---
obs0.15423 27822 99.81 %-
Solvent computationIon probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å / Solvent model: MASK
Displacement parametersBiso mean: 60.981 Å2
Baniso -1Baniso -2Baniso -3
1--1.97 Å20 Å20 Å2
2--0.02 Å20 Å2
3---1.95 Å2
Refinement stepCycle: 1 / Resolution: 2.53→50.01 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms3676 0 116 171 3963
Refine LS restraints
Refine-IDTypeDev idealDev ideal targetNumber
X-RAY DIFFRACTIONr_bond_refined_d0.0170.0193934
X-RAY DIFFRACTIONr_bond_other_d0.0020.023809
X-RAY DIFFRACTIONr_angle_refined_deg2.0522.0135337
X-RAY DIFFRACTIONr_angle_other_deg1.4938815
X-RAY DIFFRACTIONr_dihedral_angle_1_deg6.6585462
X-RAY DIFFRACTIONr_dihedral_angle_2_deg34.95324.345168
X-RAY DIFFRACTIONr_dihedral_angle_3_deg15.91215680
X-RAY DIFFRACTIONr_dihedral_angle_4_deg22.0491518
X-RAY DIFFRACTIONr_chiral_restr0.1560.2598
X-RAY DIFFRACTIONr_gen_planes_refined0.010.0214299
X-RAY DIFFRACTIONr_gen_planes_other0.0040.02883
X-RAY DIFFRACTIONr_nbd_refined
X-RAY DIFFRACTIONr_nbd_other
X-RAY DIFFRACTIONr_nbtor_refined
X-RAY DIFFRACTIONr_nbtor_other
X-RAY DIFFRACTIONr_xyhbond_nbd_refined
X-RAY DIFFRACTIONr_xyhbond_nbd_other
X-RAY DIFFRACTIONr_metal_ion_refined
X-RAY DIFFRACTIONr_metal_ion_other
X-RAY DIFFRACTIONr_symmetry_vdw_refined
X-RAY DIFFRACTIONr_symmetry_vdw_other
X-RAY DIFFRACTIONr_symmetry_hbond_refined
X-RAY DIFFRACTIONr_symmetry_hbond_other
X-RAY DIFFRACTIONr_symmetry_metal_ion_refined
X-RAY DIFFRACTIONr_symmetry_metal_ion_other
X-RAY DIFFRACTIONr_mcbond_it4.9165.6421854
X-RAY DIFFRACTIONr_mcbond_other4.9135.6381853
X-RAY DIFFRACTIONr_mcangle_it6.9128.4412314
X-RAY DIFFRACTIONr_mcangle_other6.9118.4472315
X-RAY DIFFRACTIONr_scbond_it6.6396.2862080
X-RAY DIFFRACTIONr_scbond_other6.5546.2772076
X-RAY DIFFRACTIONr_scangle_it
X-RAY DIFFRACTIONr_scangle_other9.5479.123018
X-RAY DIFFRACTIONr_long_range_B_refined16.45748.0014968
X-RAY DIFFRACTIONr_long_range_B_other16.03546.9864750
X-RAY DIFFRACTIONr_rigid_bond_restr
X-RAY DIFFRACTIONr_sphericity_free
X-RAY DIFFRACTIONr_sphericity_bonded
LS refinement shellResolution: 2.534→2.6 Å / Total num. of bins used: 20
RfactorNum. reflection% reflection
Rfree0.35 100 -
Rwork0.216 2072 -
obs--99.91 %

+
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