[English] 日本語
Yorodumi
- PDB-6dhc: X-ray structure of BACE1 in complex with a bicyclic isoxazoline c... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 6dhc
TitleX-ray structure of BACE1 in complex with a bicyclic isoxazoline carboxamide as the P3 ligand
ComponentsBeta-secretase 1
KeywordsHYDROLASE / BACE1 / Memepsin 2
Function / homology
Function and homology information


memapsin 2 / Golgi-associated vesicle lumen / signaling receptor ligand precursor processing / beta-aspartyl-peptidase activity / amyloid precursor protein catabolic process / amyloid-beta formation / membrane protein ectodomain proteolysis / cellular response to manganese ion / amyloid-beta metabolic process / prepulse inhibition ...memapsin 2 / Golgi-associated vesicle lumen / signaling receptor ligand precursor processing / beta-aspartyl-peptidase activity / amyloid precursor protein catabolic process / amyloid-beta formation / membrane protein ectodomain proteolysis / cellular response to manganese ion / amyloid-beta metabolic process / prepulse inhibition / detection of mechanical stimulus involved in sensory perception of pain / cellular response to copper ion / presynaptic modulation of chemical synaptic transmission / hippocampal mossy fiber to CA3 synapse / multivesicular body / response to lead ion / trans-Golgi network / recycling endosome / protein processing / cellular response to amyloid-beta / positive regulation of neuron apoptotic process / synaptic vesicle / late endosome / peptidase activity / amyloid-beta binding / endopeptidase activity / amyloid fibril formation / lysosome / aspartic-type endopeptidase activity / early endosome / endosome membrane / endosome / membrane raft / Amyloid fiber formation / endoplasmic reticulum lumen / axon / neuronal cell body / dendrite / Golgi apparatus / enzyme binding / cell surface / proteolysis / membrane / plasma membrane
Similarity search - Function
Beta-secretase BACE1 / Beta-secretase BACE / Memapsin-like / Eukaryotic aspartyl protease / Aspartic peptidase A1 family / Peptidase family A1 domain / Peptidase family A1 domain profile. / Cathepsin D, subunit A; domain 1 / Acid Proteases / Aspartic peptidase, active site ...Beta-secretase BACE1 / Beta-secretase BACE / Memapsin-like / Eukaryotic aspartyl protease / Aspartic peptidase A1 family / Peptidase family A1 domain / Peptidase family A1 domain profile. / Cathepsin D, subunit A; domain 1 / Acid Proteases / Aspartic peptidase, active site / Eukaryotic and viral aspartyl proteases active site. / Aspartic peptidase domain superfamily / Beta Barrel / Mainly Beta
Similarity search - Domain/homology
Chem-GHJ / UREA / Beta-secretase 1
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.85 Å
AuthorsMesecar, A.D. / Lendy, E.K.
Funding support United States, 1items
OrganizationGrant numberCountry
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)GM053386 United States
CitationJournal: Bioorg. Med. Chem. Lett. / Year: 2018
Title: Design, synthesis, X-ray studies, and biological evaluation of novel BACE1 inhibitors with bicyclic isoxazoline carboxamides as the P3 ligand.
Authors: Ghosh, A.K. / Ghosh, K. / Brindisi, M. / Lendy, E.K. / Yen, Y.C. / Kumaragurubaran, N. / Huang, X. / Tang, J. / Mesecar, A.D.
History
DepositionMay 19, 2018Deposition site: RCSB / Processing site: RCSB
Revision 1.0Jul 25, 2018Provider: repository / Type: Initial release
Revision 1.1Aug 22, 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

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Beta-secretase 1
B: Beta-secretase 1
C: Beta-secretase 1
hetero molecules


Theoretical massNumber of molelcules
Total (without water)149,52920
Polymers146,5173
Non-polymers3,01317
Water4,414245
1
A: Beta-secretase 1
hetero molecules


Theoretical massNumber of molelcules
Total (without water)49,9118
Polymers48,8391
Non-polymers1,0727
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
2
B: Beta-secretase 1
hetero molecules


Theoretical massNumber of molelcules
Total (without water)49,7916
Polymers48,8391
Non-polymers9525
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
3
C: Beta-secretase 1
hetero molecules


Theoretical massNumber of molelcules
Total (without water)49,8276
Polymers48,8391
Non-polymers9885
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
Unit cell
Length a, b, c (Å)81.987, 103.322, 100.959
Angle α, β, γ (deg.)90.00, 102.98, 90.00
Int Tables number4
Space group name H-MP1211

-
Components

-
Protein , 1 types, 3 molecules ABC

#1: Protein Beta-secretase 1 / / Aspartyl protease 2 / Asp 2 / Beta-site amyloid precursor protein cleaving enzyme 1 / Beta-site APP ...Aspartyl protease 2 / Asp 2 / Beta-site amyloid precursor protein cleaving enzyme 1 / Beta-site APP cleaving enzyme 1 / Memapsin-2 / Membrane-associated aspartic protease 2


Mass: 48838.926 Da / Num. of mol.: 3 / Fragment: residues 14-454
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: BACE1, BACE, KIAA1149 / Production host: Escherichia coli (E. coli) / References: UniProt: P56817, memapsin 2

-
Non-polymers , 5 types, 262 molecules

#2: Chemical ChemComp-GHJ / (3R,3aR,6aS)-N-[(4R,7S,8S,10R,13S)-8-hydroxy-10,17-dimethyl-7-(2-methylpropyl)-5,11,14-trioxo-13-(propan-2-yl)-2-thia-6,12,15-triazaoctadecan-4-yl]hexahydrofuro[3,2-d][1,2]oxazole-3-carboxamide


Mass: 615.825 Da / Num. of mol.: 3 / Source method: obtained synthetically / Formula: C29H53N5O7S / Feature type: SUBJECT OF INVESTIGATION
#3: Chemical
ChemComp-GOL / GLYCEROL / GLYCERIN / PROPANE-1,2,3-TRIOL / Glycerol


Mass: 92.094 Da / Num. of mol.: 9 / Source method: obtained synthetically / Formula: C3H8O3
#4: Chemical
ChemComp-URE / UREA / Urea


Mass: 60.055 Da / Num. of mol.: 4 / Source method: obtained synthetically / Formula: CH4N2O
#5: Chemical ChemComp-SO4 / SULFATE ION / Sulfate


Mass: 96.063 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: SO4
#6: Water ChemComp-HOH / water / Water


Mass: 18.015 Da / Num. of mol.: 245 / 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: 2.84 Å3/Da / Density % sol: 56.75 %
Crystal growTemperature: 298 K / Method: vapor diffusion, hanging drop / pH: 5.5
Details: 0.2 M MgSO4, 0.1 M Na citrate (pH varied from 5.0 to 6.0) and 16 % to 22 % PEG4000
PH range: 5.0 to 6.0 / Temp details: room temperature

-
Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: SYNCHROTRON / Site: APS / Beamline: 31-ID / Wavelength: 0.9793 Å
DetectorType: MARMOSAIC 225 mm CCD / Detector: CCD / Date: Apr 5, 2018
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.9793 Å / Relative weight: 1
ReflectionResolution: 2.85→98.38 Å / Num. obs: 38398 / % possible obs: 99.8 % / Redundancy: 3.8 % / CC1/2: 0.998 / Rmerge(I) obs: 0.076 / Rpim(I) all: 0.042 / Rrim(I) all: 0.082 / Net I/σ(I): 15.9
Reflection shellResolution: 2.85→2.9 Å / Redundancy: 3.8 % / Rmerge(I) obs: 0.568 / Mean I/σ(I) obs: 2.3 / Num. unique obs: 3843 / CC1/2: 0.784 / Rpim(I) all: 0.336 / Rrim(I) all: 0.661 / % possible all: 99.9

-
Processing

Software
NameVersionClassification
PHENIX(1.10_2155)refinement
MOSFLMdata reduction
SCALAdata scaling
PHENIXphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT / Resolution: 2.85→40.301 Å / SU ML: 0.34 / Cross valid method: FREE R-VALUE / σ(F): 1.35 / Phase error: 22.25 / Stereochemistry target values: ML
RfactorNum. reflection% reflection
Rfree0.2183 1900 4.95 %
Rwork0.1717 --
obs0.1741 38396 99.81 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL
Refinement stepCycle: LAST / Resolution: 2.85→40.301 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms8920 0 201 245 9366
Refine LS restraints
Refine-IDTypeDev idealNumber
X-RAY DIFFRACTIONf_bond_d0.0069344
X-RAY DIFFRACTIONf_angle_d0.86712687
X-RAY DIFFRACTIONf_dihedral_angle_d16.7075413
X-RAY DIFFRACTIONf_chiral_restr0.0521376
X-RAY DIFFRACTIONf_plane_restr0.0041621
LS refinement shell
Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkRefine-ID% reflection obs (%)
2.8502-2.92150.31151250.23612607X-RAY DIFFRACTION100
2.9215-3.00040.26921400.22832595X-RAY DIFFRACTION100
3.0004-3.08870.28551340.20742592X-RAY DIFFRACTION100
3.0887-3.18830.2861310.20342602X-RAY DIFFRACTION100
3.1883-3.30230.27731410.20162595X-RAY DIFFRACTION100
3.3023-3.43440.23451390.18142597X-RAY DIFFRACTION100
3.4344-3.59060.24691410.16492624X-RAY DIFFRACTION100
3.5906-3.77980.18241240.15462576X-RAY DIFFRACTION100
3.7798-4.01640.21491290.15272621X-RAY DIFFRACTION100
4.0164-4.32620.18841330.14382598X-RAY DIFFRACTION100
4.3262-4.76090.19271300.12862607X-RAY DIFFRACTION100
4.7609-5.44840.17691500.15952621X-RAY DIFFRACTION100
5.4484-6.85890.23251260.19422631X-RAY DIFFRACTION100
6.8589-40.30540.2091570.18882630X-RAY DIFFRACTION99

+
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