[English] 日本語
Yorodumi
- PDB-6cir: Human Cytochrome P450 17A1 in complex with inhibitor: abiraterone... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 6cir
TitleHuman Cytochrome P450 17A1 in complex with inhibitor: abiraterone C6 oxime
ComponentsSteroid 17-alpha-hydroxylase/17,20 lyase
KeywordsOXIDOREDUCTASE/OXIDOREDUCTASE INHIBITOR / CYTOCHROME P450 / P450 / CYP17A1 / P450C17 / P450 17A1 / MONOOXYGENASE / 17A-HYDROXYLASE / 17 / 20-LYASE / HEME PROTEIN / CYTOCHROME P450 OXIDOREDUCTASE / MEMBRANE / MICROSOME / ENDOPLASMIC RETICULUM / OXIDOREDUCTASE-OXIDOREDUCTASE INHIBITOR / OXIDOREDUCTASE / OXIDOREDUCTASE-OXIDOREDUCTASE 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 ...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 / 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
6-oxime-17-(3-pyridyl)-androst-16-en-3-ol / PROTOPORPHYRIN IX CONTAINING FE / Steroid 17-alpha-hydroxylase/17,20 lyase
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.648 Å
AuthorsScott, E.E. / Fehl, C.
Funding support United States, 1items
OrganizationGrant numberCountry
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)GM102505 United States
CitationJournal: J. Med. Chem. / Year: 2018
Title: Structure-Based Design of Inhibitors with Improved Selectivity for Steroidogenic Cytochrome P450 17A1 over Cytochrome P450 21A2.
Authors: Fehl, C. / Vogt, C.D. / Yadav, R. / Li, K. / Scott, E.E. / Aube, J.
History
DepositionFeb 25, 2018Deposition site: RCSB / Processing site: RCSB
Revision 1.0Jun 6, 2018Provider: repository / Type: Initial release
Revision 1.1Jun 27, 2018Group: Data collection / Database references / Category: citation
Item: _citation.journal_volume / _citation.page_first / _citation.page_last
Revision 1.2Jan 1, 2020Group: Author supporting evidence / Category: pdbx_audit_support / Item: _pdbx_audit_support.funding_organization
Revision 1.3Oct 4, 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 / pdbx_initial_refinement_model / pdbx_struct_conn_angle / 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_label_asym_id / _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 / _struct_conn.pdbx_dist_value / _struct_conn.pdbx_value_order / _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

-
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)226,94912
Polymers222,9614
Non-polymers3,9888
Water2,396133
1
A: Steroid 17-alpha-hydroxylase/17,20 lyase
hetero molecules


Theoretical massNumber of molelcules
Total (without water)56,7373
Polymers55,7401
Non-polymers9972
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
2
B: Steroid 17-alpha-hydroxylase/17,20 lyase
hetero molecules


Theoretical massNumber of molelcules
Total (without water)56,7373
Polymers55,7401
Non-polymers9972
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
3
C: Steroid 17-alpha-hydroxylase/17,20 lyase
hetero molecules


Theoretical massNumber of molelcules
Total (without water)56,7373
Polymers55,7401
Non-polymers9972
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
4
D: Steroid 17-alpha-hydroxylase/17,20 lyase
hetero molecules


Theoretical massNumber of molelcules
Total (without water)56,7373
Polymers55,7401
Non-polymers9972
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
Unit cell
Length a, b, c (Å)91.904, 151.874, 168.188
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: 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, 17alpha-hydroxyprogesterone deacetylase
#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-3NQ / 6-oxime-17-(3-pyridyl)-androst-16-en-3-ol


Mass: 380.523 Da / Num. of mol.: 4 / Source method: obtained synthetically / Formula: C24H32N2O2
#4: Water ChemComp-HOH / water / Water


Mass: 18.015 Da / Num. of mol.: 133 / 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: 2.63 Å3/Da / Density % sol: 53.27 %
Crystal growTemperature: 293 K / Method: vapor diffusion, hanging drop / pH: 8.5
Details: 0.175 M Tris, pH 8.5 containing 30% PEG 3350, 3% glycerol, and 0.250-0.275 M lithium sulfate

-
Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: SYNCHROTRON / Site: SSRL / Beamline: BL12-2 / Wavelength: 0.9795 Å
DetectorType: DECTRIS PILATUS 6M / Detector: PIXEL / Date: Feb 17, 2014
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.9795 Å / Relative weight: 1
ReflectionResolution: 2.648→39.314 Å / Num. obs: 68518 / % possible obs: 99 % / Redundancy: 6.7 % / Rpim(I) all: 0.061 / Net I/σ(I): 13.1
Reflection shellResolution: 2.65→2.79 Å / Redundancy: 6.7 % / Mean I/σ(I) obs: 1.6 / Num. unique obs: 9510 / Rpim(I) all: 0.552 / % possible all: 95.4

-
Processing

Software
NameVersionClassification
PHENIX(1.13_2998: ???)refinement
XDSdata reduction
SCALAdata scaling
PHASERphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 3SWZ

3swz


Resolution: 2.648→39.314 Å / SU ML: 0.39 / Cross valid method: FREE R-VALUE / σ(F): 1.34 / Phase error: 25.6 / Stereochemistry target values: ML
RfactorNum. reflection% reflection
Rfree0.2405 3463 5.06 %
Rwork0.187 --
obs0.1897 68391 98.85 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL
Refinement stepCycle: LAST / Resolution: 2.648→39.314 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms14931 0 284 133 15348
Refine LS restraints
Refine-IDTypeDev idealNumber
X-RAY DIFFRACTIONf_bond_d0.00215580
X-RAY DIFFRACTIONf_angle_d0.57221176
X-RAY DIFFRACTIONf_dihedral_angle_d14.0929340
X-RAY DIFFRACTIONf_chiral_restr0.0412380
X-RAY DIFFRACTIONf_plane_restr0.0032667
LS refinement shell
Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkRefine-ID% reflection obs (%)
2.6483-2.68450.35381230.31052117X-RAY DIFFRACTION82
2.6845-2.72290.38561360.28132585X-RAY DIFFRACTION100
2.7229-2.76350.38251310.27092593X-RAY DIFFRACTION100
2.7635-2.80670.31891620.26432590X-RAY DIFFRACTION100
2.8067-2.85270.34861400.25632544X-RAY DIFFRACTION100
2.8527-2.90190.35581490.24962593X-RAY DIFFRACTION100
2.9019-2.95460.29871320.23872605X-RAY DIFFRACTION100
2.9546-3.01140.33411300.23522573X-RAY DIFFRACTION99
3.0114-3.07290.27621210.23252571X-RAY DIFFRACTION98
3.0729-3.13960.2771410.22712579X-RAY DIFFRACTION99
3.1396-3.21260.28911420.22472585X-RAY DIFFRACTION100
3.2126-3.2930.30161370.22672629X-RAY DIFFRACTION100
3.293-3.38190.28421380.20342593X-RAY DIFFRACTION100
3.3819-3.48140.2991500.18952604X-RAY DIFFRACTION100
3.4814-3.59370.24581330.19162609X-RAY DIFFRACTION100
3.5937-3.7220.23121640.17372599X-RAY DIFFRACTION100
3.722-3.87090.23791260.16172623X-RAY DIFFRACTION100
3.8709-4.04690.19271270.15582614X-RAY DIFFRACTION98
4.0469-4.26010.19881480.15992606X-RAY DIFFRACTION100
4.2601-4.52660.17331290.14942665X-RAY DIFFRACTION100
4.5266-4.87550.18251440.13922632X-RAY DIFFRACTION100
4.8755-5.36510.20311450.15632655X-RAY DIFFRACTION100
5.3651-6.13890.22651370.1962670X-RAY DIFFRACTION99
6.1389-7.72470.22831330.19442706X-RAY DIFFRACTION100
7.7247-39.31850.19331450.16392788X-RAY DIFFRACTION98

+
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