[English] 日本語
Yorodumi
- PDB-4ivt: Crystal structure of BACE1 with its inhibitor -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 4ivt
TitleCrystal structure of BACE1 with its inhibitor
ComponentsBeta-secretase 1
KeywordsHYDROLASE/HYDROLASE INHIBITOR / HYDROLASE / HYDROLASE-HYDROLASE INHIBITOR complex
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 / amyloid-beta metabolic process / cellular response to manganese ion / 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 / amyloid-beta metabolic process / cellular response to manganese ion / prepulse inhibition / detection of mechanical stimulus involved in sensory perception of pain / protein serine/threonine kinase binding / cellular response to copper ion / presynaptic modulation of chemical synaptic transmission / multivesicular body / hippocampal mossy fiber to CA3 synapse / response to lead ion / trans-Golgi network / recycling endosome / protein processing / cellular response to amyloid-beta / positive regulation of neuron apoptotic process / late endosome / synaptic vesicle / peptidase activity / amyloid-beta binding / endopeptidase activity / amyloid fibril formation / aspartic-type endopeptidase activity / early endosome / lysosome / 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-VTI / Beta-secretase 1
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / molecular replacement / Resolution: 1.6 Å
AuthorsChen, T.T. / Li, L. / Chen, W.Y. / Xu, Y.C.
CitationJournal: Molecules / Year: 2013
Title: Virtual screening and structure-based discovery of indole acylguanidines as potent beta-secretase (BACE1) inhibitors
Authors: Zou, Y. / Li, L. / Chen, W.Y. / Chen, T.T. / Ma, L. / Wang, X. / Xiong, B. / Xu, Y.C. / Shen, J.
History
DepositionJan 23, 2013Deposition site: RCSB / Processing site: PDBJ
Revision 1.0Nov 13, 2013Provider: repository / Type: Initial release
Revision 1.1Nov 8, 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 / 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 / _struct_ref_seq_dif.details / _struct_site.pdbx_auth_asym_id / _struct_site.pdbx_auth_comp_id / _struct_site.pdbx_auth_seq_id
Revision 1.2Oct 30, 2024Group: Structure summary / Category: pdbx_entry_details / pdbx_modification_feature

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Beta-secretase 1
hetero molecules


Theoretical massNumber of molelcules
Total (without water)48,8474
Polymers48,2231
Non-polymers6243
Water7,440413
1


  • Idetical with deposited unit
  • defined by author
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Unit cell
Length a, b, c (Å)104.690, 128.840, 76.760
Angle α, β, γ (deg.)90.000, 90.000, 90.000
Int Tables number20
Space group name H-MC2221
Components on special symmetry positions
IDModelComponents
11A-694-

HOH

-
Components

#1: Protein Beta-secretase 1 / BACE1 / Aspartyl protease 2 / ASP2 / Asp 2 / Beta-site amyloid precursor protein cleaving enzyme 1 ...BACE1 / Aspartyl protease 2 / ASP2 / Asp 2 / Beta-site amyloid precursor protein cleaving enzyme 1 / Beta-site APP cleaving enzyme 1 / Memapsin-2 / Membrane-associated aspartic protease 2


Mass: 48222.922 Da / Num. of mol.: 1 / Fragment: UNP residues 43-454 / Mutation: K75A, E77A
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: BACE1 / Plasmid: pET28a / Production host: Escherichia coli (E. coli) / Strain (production host): BL21(DE3) / References: UniProt: P56817, memapsin 2
#2: Chemical ChemComp-VTI / N-{N-[4-(acetylamino)-3,5-dichlorobenzyl]carbamimidoyl}-2-(1H-indol-1-yl)acetamide


Mass: 432.303 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C20H19Cl2N5O2
#3: Chemical ChemComp-SO4 / SULFATE ION


Mass: 96.063 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: SO4
#4: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 413 / Source method: isolated from a natural source / Formula: H2O
Has protein modificationY

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 2.68 Å3/Da / Density % sol: 54.17 %
Crystal growTemperature: 293 K / Method: vapor diffusion, hanging drop / pH: 7.5
Details: 0.6M Li2SO4, 100mM HEPES, 25% PEG3350, pH 7.5, vapor diffusion, hanging drop, temperature 293K

-
Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: SYNCHROTRON / Site: SSRF / Beamline: BL17U / Wavelength: 0.979 Å
DetectorType: ADSC QUANTUM 315r / Detector: CCD / Date: May 12, 2011
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.979 Å / Relative weight: 1
ReflectionNumber: 495342 / Rmerge(I) obs: 0.124 / D res high: 1.6 Å / Num. obs: 68515 / % possible obs: 99.9
Diffraction reflection shell
Highest resolution (Å)Lowest resolution (Å)Num. obs% possible obs (%)IDRmerge(I) obs
1.61.64499310010.418
1.641.69491110010.372
1.691.74475610010.313
1.741.79463210010.271
1.791.85448410010.229
1.851.91433910010.199
1.911.98421610010.171
1.982.07402210010.149
2.072.16386899.910.139
2.162.26373899.910.132
2.262.39354810010.128
2.392.53334410010.122
2.532.7314810010.117
2.72.92293910010.113
2.923.2274710010.109
3.23.58247710010.104
3.584.13219110010.101
4.135.06186099.910.102
5.067.16148210010.1
ReflectionResolution: 1.6→43.25 Å / Num. obs: 68689 / % possible obs: 99.8 % / Observed criterion σ(I): -3 / Biso Wilson estimate: 21.568 Å2 / Rmerge(I) obs: 0.124 / Net I/σ(I): 10.65
Reflection shell

Diffraction-ID: 1

Resolution (Å)Highest resolution (Å)Rmerge F obsRmerge(I) obsMean I/σ(I) obsNum. measured obsNum. possibleNum. unique obsRrim(I) all% possible all
1.6-1.70.2980.3884.357796811011109530.41999.5
1.7-1.810.1950.2765.967545510331103280.297100
1.81-1.960.1270.1958.1970616965996570.21100
1.96-2.140.0870.14710.9665139891989150.158100
2.14-2.40.0730.1312.7558897808380810.14100
2.4-2.760.0610.11914.5751888716771650.128100
2.76-3.380.0510.10816.5643080608360810.116100
3.38-4.770.0460.10218.3934170478047790.11100
4.770.0480.10118.1518574277027300.1198.6

-
Phasing

PhasingMethod: molecular replacement
Phasing MRModel details: Phaser MODE: MR_AUTO
Highest resolutionLowest resolution
Rotation1.6 Å43.25 Å
Translation1.6 Å43.25 Å

-
Processing

Software
NameVersionClassificationNB
XSCALEdata scaling
PHASER2.1.4phasing
PHENIX1.8_1069refinement
PDB_EXTRACT3.11data extraction
Blu-Icedata collection
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 2B8L

2b8l


Resolution: 1.6→43.247 Å / Occupancy max: 1 / Occupancy min: 0.5 / FOM work R set: 0.8964 / SU ML: 0.12 / σ(F): 1.99 / Phase error: 17.2 / Stereochemistry target values: MLHL
RfactorNum. reflection% reflection
Rfree0.1909 2056 3 %
Rwork0.1693 --
obs0.17 68515 99.91 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL
Displacement parametersBiso max: 55.68 Å2 / Biso mean: 15.9635 Å2 / Biso min: 5.22 Å2
Refinement stepCycle: LAST / Resolution: 1.6→43.247 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms2911 0 39 413 3363
Refine LS restraints
Refine-IDTypeDev idealNumber
X-RAY DIFFRACTIONf_bond_d0.0063058
X-RAY DIFFRACTIONf_angle_d1.1494166
X-RAY DIFFRACTIONf_chiral_restr0.078454
X-RAY DIFFRACTIONf_plane_restr0.005533
X-RAY DIFFRACTIONf_dihedral_angle_d13.2431083
LS refinement shell

Refine-ID: X-RAY DIFFRACTION / Total num. of bins used: 15

Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkNum. reflection all% reflection obs (%)
1.6-1.63720.22841350.185843684503100
1.6372-1.67820.18081350.171743724507100
1.6782-1.72350.19881360.167343884524100
1.7235-1.77420.16821370.164944234560100
1.7742-1.83150.23041360.162843844520100
1.8315-1.8970.18451350.165143884523100
1.897-1.97290.1911370.163244244561100
1.9729-2.06270.18071360.160743954531100
2.0627-2.17150.18571360.160244114547100
2.1715-2.30750.18231370.162844284565100
2.3075-2.48570.17791370.174844244561100
2.4857-2.73580.21331380.179444474585100
2.7358-3.13150.16091380.180444754613100
3.1315-3.9450.18131400.166645144654100
3.945-43.26240.21611430.16914618476199

+
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