[English] 日本語
Yorodumi
- PDB-5tol: CRYSTAL STRUCTURE OF BETA-SITE APP-CLEAVING ENZYME 1 COMPLEXED WI... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 5tol
TitleCRYSTAL STRUCTURE OF BETA-SITE APP-CLEAVING ENZYME 1 COMPLEXED WITH N-(3-((4AS,7AS)-2-AMINO-4,4A,5,6-TETRAHYDRO-7AH-FURO[2,3-D][1,3]THIAZIN-7A-YL)-4-FLUOROPHENYL)-5-BROMO-2-PYRIDINECARBOXAMIDE
ComponentsBeta-secretase 1
KeywordsHYDROLASE / ASPARTYL PROTEASE / BACE1 / KIAA1149 / ASP2 / FLJ90568 / BACE / HSPC104
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 / protein serine/threonine kinase binding / 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 / late endosome / synaptic vesicle / peptidase activity / amyloid-beta binding / endopeptidase activity / amyloid fibril formation / aspartic-type endopeptidase activity / lysosome / 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-7H3 / Beta-secretase 1
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / FOURIER SYNTHESIS / Resolution: 2.51 Å
AuthorsMuckelbauer, J.K.
CitationJournal: Bioorg.Med.Chem.Lett. / Year: 2016
Title: Discovery of furo[2,3-d][1,3]thiazinamines as beta amyloid cleaving enzyme-1 (BACE1) inhibitors.
Authors: Wu, Y.J. / Guernon, J. / Rajamani, R. / Toyn, J.H. / Ahlijanian, M.K. / Albright, C.F. / Muckelbauer, J. / Chang, C. / Camac, D. / Macor, J.E. / Thompson, L.A.
History
DepositionOct 18, 2016Deposition site: RCSB / Processing site: RCSB
Revision 1.0Nov 23, 2016Provider: repository / Type: Initial release
Revision 1.1Dec 7, 2016Group: Database references

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Beta-secretase 1
hetero molecules


Theoretical massNumber of molelcules
Total (without water)46,3752
Polymers45,9241
Non-polymers4511
Water1,53185
1


  • Idetical with deposited unit
  • defined by author&software
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
Unit cell
Length a, b, c (Å)101.490, 101.490, 171.237
Angle α, β, γ (deg.)90.000, 90.000, 120.000
Int Tables number178
Space group name H-MP6122
Components on special symmetry positions
IDModelComponents
11A-612-

HOH

-
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: 45923.547 Da / Num. of mol.: 1 / Fragment: kinase domain / Mutation: R56K, R57K
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-7H3 / N-{3-[(4aR,7aR)-2-amino-4,4a,5,6-tetrahydro-7aH-furo[2,3-d][1,3]thiazin-7a-yl]-4-fluorophenyl}-5-bromopyridine-2-carboxamide


Mass: 451.313 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C18H16BrFN4O2S
#3: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 85 / 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: 2.77 Å3/Da / Density % sol: 55.62 %
Crystal growTemperature: 298 K / Method: vapor diffusion / pH: 6.4

-
Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: SYNCHROTRON / Site: APS / Beamline: 17-ID / Wavelength: 1 / Wavelength: 1 Å
DetectorType: DECTRIS PILATUS 6M / Detector: PIXEL / Date: Mar 9, 2011
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelength
IDWavelength (Å)Relative weight
111
211
ReflectionResolution: 2.51→48.65 Å / Num. obs: 18647 / % possible obs: 100 % / Observed criterion σ(I): 0 / Redundancy: 18.3 % / Rsym value: 0.088 / Net I/σ(I): 25.7
Reflection shellResolution: 2.51→2.64 Å / Redundancy: 19 % / Mean I/σ(I) obs: 5.6 / Num. unique all: 2639 / CC1/2: 0.964 / Rsym value: 0.531 / Rejects: 0 / % possible all: 100

-
Processing

Software
NameVersionClassification
REFMAC5.2.0019refinement
PDB_EXTRACT3.2data extraction
XDSdata reduction
SCALAdata scaling
RefinementMethod to determine structure: FOURIER SYNTHESIS / Resolution: 2.51→48.65 Å / Cor.coef. Fo:Fc: 0.943 / Cor.coef. Fo:Fc free: 0.921 / WRfactor Rfree: 0.2458 / WRfactor Rwork: 0.1926 / FOM work R set: 0.834 / SU B: 7.766 / SU ML: 0.176 / SU R Cruickshank DPI: 0.3735 / SU Rfree: 0.2701 / Cross valid method: THROUGHOUT / σ(F): 0 / ESU R: 0.373 / ESU R Free: 0.27 / Stereochemistry target values: MAXIMUM LIKELIHOOD
RfactorNum. reflection% reflectionSelection details
Rfree0.2569 951 5.1 %RANDOM
Rwork0.2009 ---
obs0.2037 17632 99.89 %-
Solvent computationIon probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å / Solvent model: MASK
Displacement parametersBiso max: 85.77 Å2 / Biso mean: 42.077 Å2 / Biso min: 21.23 Å2
Baniso -1Baniso -2Baniso -3
1--0.48 Å2-0.24 Å20 Å2
2---0.48 Å20 Å2
3---0.71 Å2
Refinement stepCycle: final / Resolution: 2.51→48.65 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms2885 0 27 85 2997
Biso mean--42.99 40.1 -
Num. residues----374
Refine LS restraints
Refine-IDTypeDev idealDev ideal targetNumber
X-RAY DIFFRACTIONr_bond_refined_d0.0120.0222990
X-RAY DIFFRACTIONr_angle_refined_deg1.4171.9554075
X-RAY DIFFRACTIONr_dihedral_angle_1_deg6.6535370
X-RAY DIFFRACTIONr_dihedral_angle_2_deg34.27223.516128
X-RAY DIFFRACTIONr_dihedral_angle_3_deg15.09715448
X-RAY DIFFRACTIONr_dihedral_angle_4_deg16.0361516
X-RAY DIFFRACTIONr_chiral_restr0.090.2449
X-RAY DIFFRACTIONr_gen_planes_refined0.0050.022287
X-RAY DIFFRACTIONr_nbd_refined0.2070.21203
X-RAY DIFFRACTIONr_nbtor_refined0.3170.22013
X-RAY DIFFRACTIONr_xyhbond_nbd_refined0.1540.2151
X-RAY DIFFRACTIONr_symmetry_vdw_refined0.1750.234
X-RAY DIFFRACTIONr_symmetry_hbond_refined0.2090.28
X-RAY DIFFRACTIONr_mcbond_it1.01821885
X-RAY DIFFRACTIONr_mcangle_it1.7212.52982
X-RAY DIFFRACTIONr_scbond_it2.04931276
X-RAY DIFFRACTIONr_scangle_it3.0944.51093
LS refinement shellResolution: 2.506→2.571 Å / Total num. of bins used: 20
RfactorNum. reflection% reflection
Rfree0.349 82 -
Rwork0.291 1252 -
all-1334 -
obs--100 %

+
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