[English] 日本語
Yorodumi
- PDB-4x7i: Crystal Structure of BACE with amino thiazine inhibitor LY2886721 -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 4x7i
TitleCrystal Structure of BACE with amino thiazine inhibitor LY2886721
ComponentsBeta-secretase 1
KeywordsHYDROLASE/HYDROLASE INHIBITOR / BACE / beta-secretase / inhibitor / complex / HYDROLASE-HYDROLASE INHIBITOR complex
Function / homology
Function and homology information


memapsin 2 / Golgi-associated vesicle lumen / beta-aspartyl-peptidase activity / signaling receptor ligand precursor processing / 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 / beta-aspartyl-peptidase activity / signaling receptor ligand precursor processing / 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 / cellular response to copper ion / protein serine/threonine kinase binding / presynaptic modulation of chemical synaptic transmission / multivesicular body / hippocampal mossy fiber to CA3 synapse / trans-Golgi network / response to lead ion / protein processing / recycling endosome / 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 / endosome membrane / membrane raft / Amyloid fiber formation / endoplasmic reticulum lumen / axon / neuronal cell body / dendrite / enzyme binding / cell surface / Golgi apparatus / 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-3YS / Beta-secretase 1
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / Resolution: 1.77 Å
AuthorsTimm, D.E.
CitationJournal: J.Neurosci. / Year: 2015
Title: The Potent BACE1 Inhibitor LY2886721 Elicits Robust Central A beta Pharmacodynamic Responses in Mice, Dogs, and Humans.
Authors: May, P.C. / Willis, B.A. / Lowe, S.L. / Dean, R.A. / Monk, S.A. / Cocke, P.J. / Audia, J.E. / Boggs, L.N. / Borders, A.R. / Brier, R.A. / Calligaro, D.O. / Day, T.A. / Ereshefsky, L. / ...Authors: May, P.C. / Willis, B.A. / Lowe, S.L. / Dean, R.A. / Monk, S.A. / Cocke, P.J. / Audia, J.E. / Boggs, L.N. / Borders, A.R. / Brier, R.A. / Calligaro, D.O. / Day, T.A. / Ereshefsky, L. / Erickson, J.A. / Gevorkyan, H. / Gonzales, C.R. / James, D.E. / Jhee, S.S. / Komjathy, S.F. / Li, L. / Lindstrom, T.D. / Mathes, B.M. / Martenyi, F. / Sheehan, S.M. / Stout, S.L. / Timm, D.E. / Vaught, G.M. / Watson, B.M. / Winneroski, L.L. / Yang, Z. / Mergott, D.J.
History
DepositionDec 9, 2014Deposition site: RCSB / Processing site: RCSB
Revision 1.0Dec 24, 2014Provider: repository / Type: Initial release
Revision 1.1Feb 4, 2015Group: Database references
Revision 1.2Nov 22, 2017Group: Derived calculations / Refinement description / Source and taxonomy
Category: entity_src_gen / pdbx_struct_oper_list / software
Item: _entity_src_gen.pdbx_alt_source_flag / _pdbx_struct_oper_list.symmetry_operation
Revision 1.3Oct 23, 2024Group: Data collection / Database references / Structure summary
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / database_2 / pdbx_entry_details / pdbx_modification_feature
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

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


Theoretical massNumber of molelcules
Total (without water)98,9056
Polymers97,9402
Non-polymers9654
Water15,493860
1
A: Beta-secretase 1
hetero molecules


Theoretical massNumber of molelcules
Total (without water)49,4533
Polymers48,9701
Non-polymers4832
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
2
B: Beta-secretase 1
hetero molecules


Theoretical massNumber of molelcules
Total (without water)49,4533
Polymers48,9701
Non-polymers4832
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Unit cell
Length a, b, c (Å)86.432, 89.773, 130.663
Angle α, β, γ (deg.)90.00, 90.00, 90.00
Int Tables number19
Space group name H-MP212121

-
Components

#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: 48970.117 Da / Num. of mol.: 2 / Fragment: UNP 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
#2: Chemical ChemComp-3YS / N-{3-[(4aS,7aS)-2-amino-4a,5-dihydro-4H-furo[3,4-d][1,3]thiazin-7a(7H)-yl]-4-fluorophenyl}-5-fluoropyridine-2-carboxamide


Mass: 390.407 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C18H16F2N4O2S
#3: Chemical ChemComp-GOL / GLYCEROL / GLYCERIN / PROPANE-1,2,3-TRIOL


Mass: 92.094 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C3H8O3
#4: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 860 / 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: 2.59 Å3/Da / Density % sol: 52.47 %
Crystal growTemperature: 277 K / Method: vapor diffusion, hanging drop
Details: PEG8000, sodium cacodylate, ammonium sulfate, pH 7.4

-
Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: SYNCHROTRON / Site: APS / Beamline: 31-ID / Wavelength: 0.979 Å
DetectorType: RAYONIX MX225HE / Detector: CCD / Date: Aug 11, 2014
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.979 Å / Relative weight: 1
ReflectionResolution: 1.77→130 Å / Num. obs: 99757 / % possible obs: 100 % / Redundancy: 7.3 % / Net I/σ(I): 13.2

-
Processing

Software
NameVersionClassification
REFMAC5.8.0069refinement
SCALAdata scaling
REFMACphasing
RefinementResolution: 1.77→73.99 Å / Cor.coef. Fo:Fc: 0.965 / Cor.coef. Fo:Fc free: 0.944 / SU B: 2.146 / SU ML: 0.067 / Cross valid method: THROUGHOUT / ESU R: 0.098 / ESU R Free: 0.099 / Stereochemistry target values: MAXIMUM LIKELIHOOD / Details: HYDROGENS HAVE BEEN USED IF PRESENT IN THE INPUT
RfactorNum. reflection% reflectionSelection details
Rfree0.20767 1040 1 %RANDOM
Rwork0.17263 ---
obs0.17299 98625 99.95 %-
Solvent computationIon probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å / Solvent model: BABINET MODEL WITH MASK
Displacement parametersBiso mean: 19.322 Å2
Baniso -1Baniso -2Baniso -3
1--0.66 Å2-0 Å20 Å2
2--1.37 Å2-0 Å2
3----0.72 Å2
Refinement stepCycle: 1 / Resolution: 1.77→73.99 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms6099 0 66 860 7025
Refine LS restraints
Refine-IDTypeDev idealDev ideal targetNumber
X-RAY DIFFRACTIONr_bond_refined_d0.010.0196462
X-RAY DIFFRACTIONr_bond_other_d
X-RAY DIFFRACTIONr_angle_refined_deg1.3911.9518828
X-RAY DIFFRACTIONr_angle_other_deg
X-RAY DIFFRACTIONr_dihedral_angle_1_deg6.5415815
X-RAY DIFFRACTIONr_dihedral_angle_2_deg33.54223.836292
X-RAY DIFFRACTIONr_dihedral_angle_3_deg11.815151034
X-RAY DIFFRACTIONr_dihedral_angle_4_deg18.5251537
X-RAY DIFFRACTIONr_chiral_restr0.0940.2969
X-RAY DIFFRACTIONr_gen_planes_refined0.0070.0214977
X-RAY DIFFRACTIONr_gen_planes_other
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_it1.3161.6593150
X-RAY DIFFRACTIONr_mcbond_other
X-RAY DIFFRACTIONr_mcangle_it2.2062.4753939
X-RAY DIFFRACTIONr_mcangle_other
X-RAY DIFFRACTIONr_scbond_it1.8591.873312
X-RAY DIFFRACTIONr_scbond_other
X-RAY DIFFRACTIONr_scangle_it
X-RAY DIFFRACTIONr_scangle_other
X-RAY DIFFRACTIONr_long_range_B_refined5.8715.27110991
X-RAY DIFFRACTIONr_long_range_B_other
X-RAY DIFFRACTIONr_rigid_bond_restr
X-RAY DIFFRACTIONr_sphericity_free
X-RAY DIFFRACTIONr_sphericity_bonded
LS refinement shellResolution: 1.769→1.815 Å / Total num. of bins used: 20
RfactorNum. reflection% reflection
Rfree0.284 72 -
Rwork0.23 7202 -
obs--99.99 %

+
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