[English] 日本語
Yorodumi
- PDB-5irq: Human cytochrome P450 17A1 bound to inhibitors (R)- and (S)- orteronel -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 5irq
TitleHuman cytochrome P450 17A1 bound to inhibitors (R)- and (S)- orteronel
ComponentsSteroid 17-alpha-hydroxylase/17,20 lyase
KeywordsOXIDOREDUCTASE / LYASE/INHIBITOR / Inhibitor complex / LYASE-INHIBITOR complex
Function / homology
Function and homology information


Defective CYP17A1 causes AH5 / steroid 17alpha-monooxygenase / 17alpha-hydroxyprogesterone deacetylase / steroid 17-alpha-monooxygenase activity / glucocorticoid biosynthetic process / Androgen biosynthesis / hormone biosynthetic process / Glucocorticoid biosynthesis / androgen biosynthetic process / sex differentiation ...Defective CYP17A1 causes AH5 / steroid 17alpha-monooxygenase / 17alpha-hydroxyprogesterone deacetylase / steroid 17-alpha-monooxygenase activity / glucocorticoid biosynthetic process / Androgen biosynthesis / hormone biosynthetic process / Glucocorticoid biosynthesis / androgen biosynthetic process / sex differentiation / progesterone metabolic process / steroid biosynthetic process / steroid metabolic process / oxygen binding / lyase activity / iron ion binding / axon / neuronal cell body / heme binding / endoplasmic reticulum membrane / endoplasmic reticulum
Similarity search - Function
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
(R)-orteronel / (S)-orteronel / PROTOPORPHYRIN IX CONTAINING FE / Steroid 17-alpha-hydroxylase/17,20 lyase
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / molecular replacement / Resolution: 2.202 Å
AuthorsScott, E.E. / Petrunak, E.M.
Funding support United States, 1items
OrganizationGrant numberCountry
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)5R01GM102505 United States
CitationJournal: Drug Metab. Dispos. / Year: 2017
Title: Structural and Functional Evaluation of Clinically Relevant Inhibitors of Steroidogenic Cytochrome P450 17A1.
Authors: Petrunak, E.M. / Rogers, S.A. / Aube, J. / Scott, E.E.
History
DepositionMar 14, 2016Deposition site: RCSB / Processing site: RCSB
Revision 1.0Mar 15, 2017Provider: repository / Type: Initial release
Revision 1.1Apr 19, 2017Group: Database references
Revision 1.2May 17, 2017Group: Database references
Revision 1.3Sep 13, 2017Group: Author supporting evidence / Category: pdbx_audit_support / Item: _pdbx_audit_support.funding_organization
Revision 1.4Dec 25, 2019Group: Author supporting evidence / Category: pdbx_audit_support / Item: _pdbx_audit_support.funding_organization
Revision 1.5Sep 27, 2023Group: Data collection / Database references / Refinement description
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / database_2 / pdbx_initial_refinement_model
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Steroid 17-alpha-hydroxylase/17,20 lyase
B: Steroid 17-alpha-hydroxylase/17,20 lyase
C: Steroid 17-alpha-hydroxylase/17,20 lyase
D: Steroid 17-alpha-hydroxylase/17,20 lyase
hetero molecules


Theoretical massNumber of molelcules
Total (without water)226,65612
Polymers222,9614
Non-polymers3,6958
Water9,458525
1
A: Steroid 17-alpha-hydroxylase/17,20 lyase
hetero molecules


Theoretical massNumber of molelcules
Total (without water)56,6643
Polymers55,7401
Non-polymers9242
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
2
B: Steroid 17-alpha-hydroxylase/17,20 lyase
hetero molecules


Theoretical massNumber of molelcules
Total (without water)56,6643
Polymers55,7401
Non-polymers9242
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
3
C: Steroid 17-alpha-hydroxylase/17,20 lyase
hetero molecules


Theoretical massNumber of molelcules
Total (without water)56,6643
Polymers55,7401
Non-polymers9242
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
4
D: Steroid 17-alpha-hydroxylase/17,20 lyase
hetero molecules


Theoretical massNumber of molelcules
Total (without water)56,6643
Polymers55,7401
Non-polymers9242
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Unit cell
Length a, b, c (Å)90.168, 153.204, 168.119
Angle α, β, γ (deg.)90.00, 90.00, 90.00
Int Tables number19
Space group name H-MP212121

-
Components

#1: Protein
Steroid 17-alpha-hydroxylase/17,20 lyase / 17-alpha-hydroxyprogesterone aldolase / CYPXVII / Cytochrome P450 17A1 / Cytochrome P450-C17 / ...17-alpha-hydroxyprogesterone aldolase / CYPXVII / Cytochrome P450 17A1 / Cytochrome P450-C17 / Cytochrome P450c17 / Steroid 17-alpha-monooxygenase


Mass: 55740.141 Da / Num. of mol.: 4 / Fragment: UNP residues 24-508
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: CYP17A1, CYP17, S17AH / Production host: Escherichia coli (E. coli)
References: UniProt: P05093, steroid 17alpha-monooxygenase, EC: 4.1.2.30
#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-6D7 / (R)-orteronel / 6-[(7R)-7-hydroxy-6,7-dihydro-5H-pyrrolo[1,2-c]imidazol-7-yl]-N-methylnaphthalene-2-carboxamide


Mass: 307.346 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C18H17N3O2
#4: Chemical ChemComp-7D6 / (S)-orteronel / 6-[(7S)-7-hydroxy-6,7-dihydro-5H-pyrrolo[1,2-c]imidazol-7-yl]-N-methylnaphthalene-2-carboxamide


Mass: 307.346 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C18H17N3O2
#5: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 525 / 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: 2.6 Å3/Da / Density % sol: 52.77 %
Crystal growTemperature: 293 K / Method: vapor diffusion, hanging drop
Details: 175 mM Tris-HCl, pH 8.0, 30% w/v PEG3350, 200 mM lithium sulfate, 12% glycerol

-
Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: SYNCHROTRON / Site: SSRL / Beamline: BL7-1 / Wavelength: 0.9795 Å
DetectorType: ADSC QUANTUM 315r / Detector: CCD / Date: Apr 11, 2014
RadiationMonochromator: Side-scattering I-beam bent single crystal, asymmetric cut 4.9650 degrees
Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.9795 Å / Relative weight: 1
ReflectionResolution: 2.202→39.285 Å / Num. obs: 118120 / % possible obs: 99.8 % / Redundancy: 7.4 % / Biso Wilson estimate: 37.19 Å2 / Rsym value: 0.134 / Net I/av σ(I): 5.511 / Net I/σ(I): 14
Reflection shellResolution: 2.202→2.32 Å / Redundancy: 7.4 % / Mean I/σ(I) obs: 0.5 / % possible all: 99

-
Phasing

PhasingMethod: molecular replacement

-
Processing

Software
NameVersionClassification
PHENIX(1.10pre_2124: ???)refinement
SCALA3.3.20data scaling
PHASERphasing
PDB_EXTRACT3.2data extraction
XDSdata reduction
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: PDB entry 3SWZ

3swz


Resolution: 2.202→39.285 Å / SU ML: 0.28 / Cross valid method: FREE R-VALUE / σ(F): 1.33 / Phase error: 26.22 / Stereochemistry target values: ML
RfactorNum. reflection% reflectionSelection details
Rfree0.2486 5913 5.01 %5
Rwork0.2013 ---
obs0.2037 117964 99.83 %-
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL
Refinement stepCycle: LAST / Resolution: 2.202→39.285 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms14901 0 264 525 15690
Refine LS restraints
Refine-IDTypeDev idealNumber
X-RAY DIFFRACTIONf_bond_d0.00515531
X-RAY DIFFRACTIONf_angle_d0.61821095
X-RAY DIFFRACTIONf_dihedral_angle_d12.4669291
X-RAY DIFFRACTIONf_chiral_restr0.0422352
X-RAY DIFFRACTIONf_plane_restr0.0032670
LS refinement shell
Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkRefine-ID% reflection obs (%)
2.2024-2.22750.33562080.30833504X-RAY DIFFRACTION96
2.2275-2.25370.31351910.29213743X-RAY DIFFRACTION100
2.2537-2.28120.30941940.283663X-RAY DIFFRACTION100
2.2812-2.310.34652150.27463701X-RAY DIFFRACTION100
2.31-2.34040.28771870.26283686X-RAY DIFFRACTION100
2.3404-2.37250.30142210.26363697X-RAY DIFFRACTION100
2.3725-2.40640.31181940.26063676X-RAY DIFFRACTION100
2.4064-2.44230.29971890.2523744X-RAY DIFFRACTION100
2.4423-2.48040.31542160.25323646X-RAY DIFFRACTION100
2.4804-2.52110.30991950.24453748X-RAY DIFFRACTION100
2.5211-2.56460.31251950.2433666X-RAY DIFFRACTION100
2.5646-2.61120.27982050.23833710X-RAY DIFFRACTION100
2.6112-2.66140.28011960.23633748X-RAY DIFFRACTION100
2.6614-2.71570.31121840.23633728X-RAY DIFFRACTION100
2.7157-2.77470.32671960.23693704X-RAY DIFFRACTION100
2.7747-2.83930.2691900.22323734X-RAY DIFFRACTION100
2.8393-2.91030.26851900.21633739X-RAY DIFFRACTION100
2.9103-2.98890.27071950.21733708X-RAY DIFFRACTION100
2.9889-3.07680.282180.22253713X-RAY DIFFRACTION100
3.0768-3.17610.26451930.21973740X-RAY DIFFRACTION100
3.1761-3.28960.2752040.22233729X-RAY DIFFRACTION100
3.2896-3.42120.26571830.21073751X-RAY DIFFRACTION100
3.4212-3.57680.24151990.19433763X-RAY DIFFRACTION100
3.5768-3.76520.19871760.19423777X-RAY DIFFRACTION100
3.7652-4.00090.22971880.17253755X-RAY DIFFRACTION100
4.0009-4.30950.20022130.16263784X-RAY DIFFRACTION100
4.3095-4.74250.19791820.15123819X-RAY DIFFRACTION100
4.7425-5.42720.21241940.15843802X-RAY DIFFRACTION100
5.4272-6.83190.24191930.19623868X-RAY DIFFRACTION100
6.8319-39.2910.1882090.15934005X-RAY DIFFRACTION100

+
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