[English] 日本語
Yorodumi
- PDB-8ss0: Human sterol 14 alpha-demethylase (CYP51) in complex with the rea... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 8ss0
TitleHuman sterol 14 alpha-demethylase (CYP51) in complex with the reaction intermediate 14 alpha-aldehyde dihydrolanosterol
ComponentsLanosterol 14-alpha demethylase
KeywordsOXIDOREDUCTASE / MONOOXYGENASE / CYTOCHROME P450 / CYP51 / ENDOPLASMIC RETICULUM / STEROL BIOSYNTHESIS
Function / homology
Function and homology information


sterol 14alpha-demethylase / sterol 14-demethylase activity / steroid 7-alpha-hydroxylase activity / oxysterol 7-alpha-hydroxylase activity / negative regulation of amyloid-beta clearance / sterol metabolic process / Cholesterol biosynthesis / bile acid biosynthetic process / EGR2 and SOX10-mediated initiation of Schwann cell myelination / steroid biosynthetic process ...sterol 14alpha-demethylase / sterol 14-demethylase activity / steroid 7-alpha-hydroxylase activity / oxysterol 7-alpha-hydroxylase activity / negative regulation of amyloid-beta clearance / sterol metabolic process / Cholesterol biosynthesis / bile acid biosynthetic process / EGR2 and SOX10-mediated initiation of Schwann cell myelination / steroid biosynthetic process / cholesterol biosynthetic process / negative regulation of protein secretion / Endogenous sterols / Activation of gene expression by SREBF (SREBP) / cholesterol homeostasis / negative regulation of protein catabolic process / oxidoreductase activity / iron ion binding / heme binding / endoplasmic reticulum membrane / membrane
Similarity search - Function
Cytochrome P450, E-class, group IV / Cytochrome P450, conserved site / Cytochrome P450 cysteine heme-iron ligand signature. / Cytochrome P450 / Cytochrome P450 superfamily / Cytochrome P450
Similarity search - Domain/homology
PROTOPORPHYRIN IX CONTAINING FE / Chem-WQR / Lanosterol 14-alpha demethylase
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.25 Å
AuthorsHargrove, T.Y. / Wawrzak, Z. / Guengerich, F.P. / Lepesheva, G.I.
Funding support United States, 1items
OrganizationGrant numberCountry
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)GM067871 United States
CitationJournal: Angew.Chem.Int.Ed.Engl. / Year: 2024
Title: Oxygen-18 Labeling Reveals a Mixed Fe-O Mechanism in the Last Step of Cytochrome P450 51 Sterol 14 alpha-Demethylation.
Authors: McCarty, K.D. / Tateishi, Y. / Hargrove, T.Y. / Lepesheva, G.I. / Guengerich, F.P.
History
DepositionMay 8, 2023Deposition site: RCSB / Processing site: RCSB
Revision 1.0Jan 17, 2024Provider: repository / Type: Initial release
Revision 1.1Jan 24, 2024Group: Database references / Category: citation
Item: _citation.page_first / _citation.page_last ..._citation.page_first / _citation.page_last / _citation.pdbx_database_id_PubMed / _citation.title
Revision 1.2Mar 6, 2024Group: Database references / Category: citation / citation_author
Item: _citation.journal_volume / _citation_author.identifier_ORCID

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Lanosterol 14-alpha demethylase
B: Lanosterol 14-alpha demethylase
hetero molecules


Theoretical massNumber of molelcules
Total (without water)106,8336
Polymers104,7182
Non-polymers2,1144
Water1,928107
1
A: Lanosterol 14-alpha demethylase
hetero molecules


Theoretical massNumber of molelcules
Total (without water)53,4163
Polymers52,3591
Non-polymers1,0572
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
2
B: Lanosterol 14-alpha demethylase
hetero molecules


Theoretical massNumber of molelcules
Total (without water)53,4163
Polymers52,3591
Non-polymers1,0572
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Unit cell
Length a, b, c (Å)145.803, 145.803, 261.161
Angle α, β, γ (deg.)90.00, 90.00, 120.00
Int Tables number180
Space group name H-MP6222
Components on special symmetry positions
IDModelComponents
11B-761-

HOH

-
Components

#1: Protein Lanosterol 14-alpha demethylase / LDM / CYPLI / Cytochrome P450 51A1 / CYP51A1 / Cytochrome P450-14DM / Cytochrome P45014DM / ...LDM / CYPLI / Cytochrome P450 51A1 / CYP51A1 / Cytochrome P450-14DM / Cytochrome P45014DM / Cytochrome P450LI / Sterol 14-alpha demethylase


Mass: 52359.113 Da / Num. of mol.: 2 / Mutation: D231A, H314A
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: CYP51A1, CYP51 / Plasmid: pCW / Production host: Escherichia coli (E. coli) / Strain (production host): HMS174 / References: UniProt: Q16850, sterol 14alpha-demethylase
#2: Chemical ChemComp-HEM / PROTOPORPHYRIN IX CONTAINING FE / HEME


Mass: 616.487 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C34H32FeN4O4
#3: Chemical ChemComp-WQR / 3beta-hydroxy-10alpha,13alpha-lanosta-8,24-dien-30-al


Mass: 440.701 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C30H48O2 / Feature type: SUBJECT OF INVESTIGATION
#4: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 107 / Source method: isolated from a natural source / Formula: H2O
Has ligand of interestY

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 3.83 Å3/Da / Density % sol: 67.85 %
Crystal growTemperature: 290 K / Method: vapor diffusion, hanging drop / pH: 7.4
Details: CALCIUM ACATATE, PEG 4000, ANAPOE 80, 14 ALPHA ALDEHYDE DERIVATIVE OD DIHYDROLANOSTEROL

-
Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: APS / Beamline: 21-ID-D / Wavelength: 1.12713 Å
DetectorType: DECTRIS EIGER X 9M / Detector: PIXEL / Date: Apr 6, 2023 / Details: Focusing Mirrors
RadiationMonochromator: Si (111) / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1.12713 Å / Relative weight: 1
ReflectionResolution: 2.25→19.89 Å / Num. obs: 36891 / % possible obs: 94.9 % / Redundancy: 4.4 % / Biso Wilson estimate: 33 Å2 / CC1/2: 0.997 / Rmerge(I) obs: 0.085 / Rrim(I) all: 0.097 / Net I/σ(I): 5.8
Reflection shellResolution: 2.25→2.5 Å / Redundancy: 3.6 % / Rmerge(I) obs: 0.602 / Mean I/σ(I) obs: 1.9 / Num. unique obs: 1845 / CC1/2: 0.848 / Rpim(I) all: 0.356 / Rrim(I) all: 0.705 / % possible all: 83.6

-
Processing

Software
NameVersionClassification
REFMAC5.8.0405refinement
HKL-2000data reduction
HKL-2000data scaling
PHASERphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 6uez

6uez


Resolution: 2.25→19.89 Å / Cor.coef. Fo:Fc: 0.937 / Cor.coef. Fo:Fc free: 0.933 / SU B: 6.623 / SU ML: 0.16 / Cross valid method: THROUGHOUT / ESU R: 0.743 / ESU R Free: 0.309 / Stereochemistry target values: MAXIMUM LIKELIHOOD / Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS
RfactorNum. reflection% reflectionSelection details
Rfree0.249 1827 5 %RANDOM
Rwork0.219 ---
obs0.219 35064 47.5 %-
Solvent computationIon probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å / Solvent model: MASK
Displacement parametersBiso mean: 37.13 Å2
Baniso -1Baniso -2Baniso -3
1-0.02 Å20.01 Å20 Å2
2--0.02 Å20 Å2
3----0.06 Å2
Refinement stepCycle: LAST / Resolution: 2.25→19.89 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms7122 0 150 107 7379
Refine LS restraints
Refine-IDTypeDev idealDev ideal targetNumber
X-RAY DIFFRACTIONr_bond_refined_d0.0070.0127492
X-RAY DIFFRACTIONr_bond_other_d0.0020.0167142
X-RAY DIFFRACTIONr_angle_refined_deg1.4461.68810195
X-RAY DIFFRACTIONr_angle_other_deg0.511.60516462
X-RAY DIFFRACTIONr_dihedral_angle_1_deg7.2525885
X-RAY DIFFRACTIONr_dihedral_angle_2_deg7.854548
X-RAY DIFFRACTIONr_dihedral_angle_3_deg17.354101275
X-RAY DIFFRACTIONr_dihedral_angle_4_deg
X-RAY DIFFRACTIONr_chiral_restr0.0640.21094
X-RAY DIFFRACTIONr_gen_planes_refined0.0060.028603
X-RAY DIFFRACTIONr_gen_planes_other0.0030.021753
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_it3.1823.5583549
X-RAY DIFFRACTIONr_mcbond_other3.183.5583549
X-RAY DIFFRACTIONr_mcangle_it5.1036.3834431
X-RAY DIFFRACTIONr_mcangle_other5.1036.3844432
X-RAY DIFFRACTIONr_scbond_it3.8373.8833943
X-RAY DIFFRACTIONr_scbond_other3.8373.8823944
X-RAY DIFFRACTIONr_scangle_it
X-RAY DIFFRACTIONr_scangle_other6.4116.9265765
X-RAY DIFFRACTIONr_long_range_B_refined9.27433.398624
X-RAY DIFFRACTIONr_long_range_B_other9.27533.398621
X-RAY DIFFRACTIONr_rigid_bond_restr
X-RAY DIFFRACTIONr_sphericity_free
X-RAY DIFFRACTIONr_sphericity_bonded
LS refinement shellResolution: 2.26→2.31 Å / Total num. of bins used: 20
RfactorNum. reflection% reflection
Rfree0.361 9 -
Rwork0.366 169 -
obs--3.19 %

+
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://pdbjlvh1.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