[English] 日本語
Yorodumi
- PDB-3t3r: Human Cytochrome P450 2A6 in complex with Pilocarpine -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 3t3r
TitleHuman Cytochrome P450 2A6 in complex with Pilocarpine
ComponentsCytochrome P450 2A6
KeywordsOXIDOREDUCTASE / CYP2A6 / cytochrome P450 2A6 / P450 2A6 / heme protein / monooxygenase / drug metabolism / xenobiotic metabolism / endoplasmic reticulum / membrane
Function / homology
Function and homology information


coumarin catabolic process / coumarin 7-hydroxylase activity / coumarin metabolic process / arachidonic acid epoxygenase activity / 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 / epoxygenase P450 pathway / 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 / cytoplasmic microtubule ...coumarin catabolic process / coumarin 7-hydroxylase activity / coumarin metabolic process / arachidonic acid epoxygenase activity / 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 / epoxygenase P450 pathway / 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 / cytoplasmic microtubule / steroid metabolic process / xenobiotic catabolic process / xenobiotic metabolic process / iron ion binding / intracellular membrane-bounded organelle / heme binding / endoplasmic reticulum membrane / enzyme binding / cytoplasm
Similarity search - Function
Cytochrome P450, E-class, group I, CYP2A-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
Chem-9PL / PROTOPORPHYRIN IX CONTAINING FE / Cytochrome P450 2A6
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.4 Å
AuthorsDeVore, N.M. / Scott, E.E.
CitationJournal: Febs J. / Year: 2012
Title: Structural comparison of cytochromes P450 2A6, 2A13, and 2E1 with pilocarpine.
Authors: DeVore, N.M. / Meneely, K.M. / Bart, A.G. / Stephens, E.S. / Battaile, K.P. / Scott, E.E.
History
DepositionJul 25, 2011Deposition site: RCSB / Processing site: RCSB
Revision 1.0Dec 7, 2011Provider: repository / Type: Initial release
Revision 1.1Jun 6, 2012Group: Database references
Revision 1.2Nov 8, 2017Group: Advisory / Refinement description / Category: pdbx_unobs_or_zero_occ_atoms / software / Item: _software.name
Revision 1.3Sep 13, 2023Group: Advisory / Data collection ...Advisory / Data collection / Database references / Derived calculations / Refinement description
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / database_2 / pdbx_initial_refinement_model / pdbx_struct_conn_angle / pdbx_unobs_or_zero_occ_atoms / struct_conn / struct_ref_seq_dif / struct_site
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_label_asym_id / _pdbx_struct_conn_angle.ptnr2_auth_asym_id / _pdbx_struct_conn_angle.ptnr2_label_asym_id / _pdbx_struct_conn_angle.ptnr3_auth_asym_id / _pdbx_struct_conn_angle.ptnr3_label_asym_id / _pdbx_struct_conn_angle.value / _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.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_ref_seq_dif.details / _struct_site.pdbx_auth_asym_id / _struct_site.pdbx_auth_comp_id / _struct_site.pdbx_auth_seq_id

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Cytochrome P450 2A6
B: Cytochrome P450 2A6
C: Cytochrome P450 2A6
D: Cytochrome P450 2A6
hetero molecules


Theoretical massNumber of molelcules
Total (without water)221,98612
Polymers218,6874
Non-polymers3,2998
Water3,909217
1
A: Cytochrome P450 2A6
hetero molecules


Theoretical massNumber of molelcules
Total (without water)55,4963
Polymers54,6721
Non-polymers8252
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
2
B: Cytochrome P450 2A6
hetero molecules


Theoretical massNumber of molelcules
Total (without water)55,4963
Polymers54,6721
Non-polymers8252
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
3
C: Cytochrome P450 2A6
hetero molecules


Theoretical massNumber of molelcules
Total (without water)55,4963
Polymers54,6721
Non-polymers8252
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
4
D: Cytochrome P450 2A6
hetero molecules


Theoretical massNumber of molelcules
Total (without water)55,4963
Polymers54,6721
Non-polymers8252
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
Unit cell
Length a, b, c (Å)70.336, 158.005, 104.453
Angle α, β, γ (deg.)90.00, 92.10, 90.00
Int Tables number4
Space group name H-MP1211

-
Components

#1: Protein
Cytochrome P450 2A6 / CYPIIA6 / Coumarin 7-hydroxylase / Cytochrome P450 IIA3 / Cytochrome P450(I)


Mass: 54671.637 Da / Num. of mol.: 4 / Fragment: unp residues 29-494 / Mutation: Y392F
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: CYP2A3, CYP2A6 / Plasmid: pKK2A6dH / Production host: Escherichia coli (E. coli) / Strain (production host): TOPP3 / References: UniProt: P11509, unspecific monooxygenase
#2: Chemical
ChemComp-HEM / PROTOPORPHYRIN IX CONTAINING FE / HEME / Heme B


Mass: 616.487 Da / Num. of mol.: 4 / Source method: obtained synthetically / Formula: C34H32FeN4O4
#3: Chemical
ChemComp-9PL / (3S,4R)-3-ethyl-4-[(1-methyl-1H-imidazol-5-yl)methyl]dihydrofuran-2(3H)-one / PILOCARPINE / Pilocarpine


Mass: 208.257 Da / Num. of mol.: 4 / Source method: obtained synthetically / Formula: C11H16N2O2 / Comment: medication*YM
#4: Water ChemComp-HOH / water / Water


Mass: 18.015 Da / Num. of mol.: 217 / Source method: isolated from a natural source / Formula: H2O
Sequence detailsAUTHORS STATE THAT THE AMINOACID AT POSITION 392 OF THE UNIPROT ENTRY P11509 SHOULD BE A TYR

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 2.65 Å3/Da / Density % sol: 53.62 %
Crystal growTemperature: 298 K / Method: vapor diffusion, hanging drop / pH: 8.5
Details: 30% PEG 3350, 0.175 M Tris, pH 8.5, 0.20 M ammomium sulfate, VAPOR DIFFUSION, HANGING DROP, temperature 298K

-
Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: SYNCHROTRON / Site: SSRL / Beamline: BL9-2 / Wavelength: 0.98 Å
DetectorType: MARMOSAIC 325 mm CCD / Detector: CCD / Date: Jun 28, 2008 / Details: Rh coated flat mirror, toroidal focusing mirror
RadiationMonochromator: Double crystal monochromator / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.98 Å / Relative weight: 1
ReflectionResolution: 2.4→87.04 Å / Num. all: 237442 / Num. obs: 85624 / % possible obs: 96.5 % / Observed criterion σ(F): 0 / Observed criterion σ(I): 0 / Redundancy: 2.8 % / Biso Wilson estimate: 41.4 Å2 / Rmerge(I) obs: 0.075 / Rsym value: 0.106 / Net I/σ(I): 13.2
Reflection shellResolution: 2.4→2.46 Å / Redundancy: 2.7 % / Rmerge(I) obs: 0.402 / Mean I/σ(I) obs: 3.4 / Num. unique all: 17456 / % possible all: 97.9

-
Processing

Software
NameVersionClassification
Blu-Icedata collection
PHASERMRphasing
REFMAC5.5.0072refinement
MOSFLMdata reduction
SCALAdata scaling
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: CYP2A6 PDB entry 1Z10

1z10


Resolution: 2.4→79 Å / Cor.coef. Fo:Fc: 0.935 / Cor.coef. Fo:Fc free: 0.893 / SU B: 8.008 / SU ML: 0.191 / Cross valid method: THROUGHOUT / σ(F): 0 / ESU R Free: 0.281
Stereochemistry target values: MAXIMUM LIKELIHOOD WITH PHASES
RfactorNum. reflection% reflectionSelection details
Rfree0.26029 4277 5 %RANDOM
Rwork0.19898 ---
all0.20215 81313 --
obs0.20215 81313 96.29 %-
Solvent computationIon probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.4 Å / Solvent model: MASK
Displacement parametersBiso mean: 30.545 Å2
Baniso -1Baniso -2Baniso -3
1-0.01 Å2-0 Å2-0 Å2
2---0.01 Å2-0 Å2
3---0 Å2
Refine analyzeLuzzati coordinate error obs: 0.277 Å
Refinement stepCycle: LAST / Resolution: 2.4→79 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms14998 0 232 217 15447
Refine LS restraints
Refine-IDTypeDev idealDev ideal targetNumber
X-RAY DIFFRACTIONr_bond_refined_d0.020.02215689
X-RAY DIFFRACTIONr_angle_refined_deg1.8472.00121205
X-RAY DIFFRACTIONr_dihedral_angle_1_deg7.15251865
X-RAY DIFFRACTIONr_dihedral_angle_2_deg35.96423.286773
X-RAY DIFFRACTIONr_dihedral_angle_3_deg19.049152748
X-RAY DIFFRACTIONr_dihedral_angle_4_deg19.70315131
X-RAY DIFFRACTIONr_chiral_restr0.1340.22209
X-RAY DIFFRACTIONr_gen_planes_refined0.0080.02112093
X-RAY DIFFRACTIONr_mcbond_it0.8711.59257
X-RAY DIFFRACTIONr_mcangle_it1.608215012
X-RAY DIFFRACTIONr_scbond_it2.63636432
X-RAY DIFFRACTIONr_scangle_it4.0884.56185
LS refinement shellResolution: 2.4→2.462 Å / Total num. of bins used: 20
RfactorNum. reflection% reflection
Rfree0.291 317 -
Rwork0.218 6095 -
obs--97.8 %

+
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