[English] 日本語
Yorodumi
- PDB-5t1w: Aminomethyl-Derived Beta Secretase (BACE1) Inhibitors: Engaging G... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 5t1w
TitleAminomethyl-Derived Beta Secretase (BACE1) Inhibitors: Engaging Gly230 without an Anilide Functionality
ComponentsBeta-secretase 1
KeywordsHYDROLASE/HYDROLASE inhibitor / beta secretase / alzheimer's / inhibitor / 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 / detection of mechanical stimulus involved in sensory perception of pain / amyloid-beta metabolic process / cellular response to manganese ion ...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 / detection of mechanical stimulus involved in sensory perception of pain / amyloid-beta metabolic process / cellular response to manganese ion / prepulse inhibition / 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 / positive regulation of neuron apoptotic process / cellular response to amyloid-beta / late endosome / synaptic vesicle / 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-74B / IODIDE ION / Beta-secretase 1
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / Resolution: 2.96 Å
AuthorsParris, K.D. / Vajdos, F.
CitationJournal: J. Med. Chem. / Year: 2017
Title: Aminomethyl-Derived Beta Secretase (BACE1) Inhibitors: Engaging Gly230 without an Anilide Functionality.
Authors: Butler, C.R. / Ogilvie, K. / Martinez-Alsina, L. / Barreiro, G. / Beck, E.M. / Nolan, C.E. / Atchison, K. / Benvenuti, E. / Buzon, L. / Doran, S. / Gonzales, C. / Helal, C.J. / Hou, X. / ...Authors: Butler, C.R. / Ogilvie, K. / Martinez-Alsina, L. / Barreiro, G. / Beck, E.M. / Nolan, C.E. / Atchison, K. / Benvenuti, E. / Buzon, L. / Doran, S. / Gonzales, C. / Helal, C.J. / Hou, X. / Hsu, M.H. / Johnson, E.F. / Lapham, K. / Lanyon, L. / Parris, K. / O'Neill, B.T. / Riddell, D. / Robshaw, A. / Vajdos, F. / Brodney, M.A.
History
DepositionAug 22, 2016Deposition site: RCSB / Processing site: RCSB
Revision 1.0Jan 11, 2017Provider: repository / Type: Initial release
Revision 1.1Jan 25, 2017Group: 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)47,72013
Polymers46,4411
Non-polymers1,27912
Water00
1


  • Idetical with deposited unit
  • defined by author&software
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
Unit cell
Length a, b, c (Å)101.460, 101.460, 170.660
Angle α, β, γ (deg.)90.000, 90.000, 120.000
Int Tables number178
Space group name H-MP6122

-
Components

-
Protein , 1 types, 1 molecules A

#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: 46440.980 Da / Num. of mol.: 1 / Fragment: UNP residues 46-454
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 , 6 types, 12 molecules

#2: Chemical ChemComp-74B / (4aR,6R,8aS)-8a-(2,4-difluoro-5-{[(2,2,2-trifluoroethyl)amino]methyl}phenyl)-6-(fluoromethyl)-4,4a,5,6,8,8a-hexahydropyrano[3,4-d][1,3]thiazin-2-amine


Mass: 427.408 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C17H19F6N3OS
#3: Chemical ChemComp-IOD / IODIDE ION


Mass: 126.904 Da / Num. of mol.: 3 / Source method: obtained synthetically / Formula: I
#4: Chemical ChemComp-NA / SODIUM ION


Mass: 22.990 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: Na
#5: Chemical ChemComp-GOL / GLYCEROL / GLYCERIN / PROPANE-1,2,3-TRIOL


Mass: 92.094 Da / Num. of mol.: 3 / Source method: obtained synthetically / Formula: C3H8O3
#6: Chemical ChemComp-DMS / DIMETHYL SULFOXIDE


Mass: 78.133 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C2H6OS / Comment: DMSO, precipitant*YM
#7: Chemical ChemComp-CL / CHLORIDE ION


Mass: 35.453 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: Cl

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 2.73 Å3/Da / Density % sol: 54.95 %
Crystal growTemperature: 293 K / Method: vapor diffusion, hanging drop
Details: 20-22.5% (w/v) PEG 5000 monomethylethyl (MME), 200 mM sodium citrate (pH 6.6), 200 mM ammonium iodide

-
Data collection

DiffractionMean temperature: 93 K
Diffraction sourceSource: ROTATING ANODE / Type: RIGAKU FR-E SUPERBRIGHT / Wavelength: 1.5 Å
DetectorType: RIGAKU SATURN 944 / Detector: CCD / Date: Oct 20, 2012
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1.5 Å / Relative weight: 1
ReflectionResolution: 2.962→170.66 Å / Num. obs: 11450 / % possible obs: 100 % / Redundancy: 17.1 % / Biso Wilson estimate: 48.64 Å2 / Rmerge(I) obs: 0.244 / Rpim(I) all: 0.06 / Rrim(I) all: 0.252 / Net I/σ(I): 14.2 / Num. measured all: 195672
Reflection shell

Diffraction-ID: 1 / Rejects: _ / % possible all: 100

Resolution (Å)Redundancy (%)Rmerge(I) obsNum. measured allNum. unique allRpim(I) allRrim(I) allNet I/σ(I) obs
2.962-2.97217.80.66620471150.1610.6865.3
13.746-170.6610.60.07417211630.0210.07725.3

-
Processing

Software
NameVersionClassification
SCALAdata scaling
BUSTER-TNT2.11.2refinement
PDB_EXTRACT3.2data extraction
HKL-2000data reduction
RefinementResolution: 2.96→32.65 Å / Cor.coef. Fo:Fc: 0.9168 / Cor.coef. Fo:Fc free: 0.8252 / Cross valid method: THROUGHOUT / σ(F): 0 / SU Rfree Blow DPI: 0.377
RfactorNum. reflection% reflectionSelection details
Rfree0.2499 543 4.77 %RANDOM
Rwork0.1782 ---
obs0.1816 11383 99.75 %-
Displacement parametersBiso max: 86.86 Å2 / Biso mean: 16.88 Å2 / Biso min: 3 Å2
Baniso -1Baniso -2Baniso -3
1--0.6049 Å20 Å20 Å2
2---0.6049 Å20 Å2
3---1.2099 Å2
Refine analyzeLuzzati coordinate error obs: 0.339 Å
Refinement stepCycle: final / Resolution: 2.96→32.65 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms2909 0 57 0 2966
Biso mean--26.33 --
Num. residues----371
Refine LS restraints
Refine-IDTypeNumberRestraint functionWeightDev ideal
X-RAY DIFFRACTIONt_dihedral_angle_d1017SINUSOIDAL2
X-RAY DIFFRACTIONt_trig_c_planes66HARMONIC2
X-RAY DIFFRACTIONt_gen_planes452HARMONIC5
X-RAY DIFFRACTIONt_it3042HARMONIC20
X-RAY DIFFRACTIONt_nbd0SEMIHARMONIC5
X-RAY DIFFRACTIONt_improper_torsion
X-RAY DIFFRACTIONt_pseud_angle
X-RAY DIFFRACTIONt_chiral_improper_torsion387SEMIHARMONIC5
X-RAY DIFFRACTIONt_sum_occupancies
X-RAY DIFFRACTIONt_utility_distance
X-RAY DIFFRACTIONt_utility_angle
X-RAY DIFFRACTIONt_utility_torsion
X-RAY DIFFRACTIONt_ideal_dist_contact3469SEMIHARMONIC4
X-RAY DIFFRACTIONt_bond_d3042HARMONIC20.01
X-RAY DIFFRACTIONt_angle_deg4135HARMONIC21.21
X-RAY DIFFRACTIONt_omega_torsion3.28
X-RAY DIFFRACTIONt_other_torsion18.62
LS refinement shellResolution: 2.96→3.24 Å / Total num. of bins used: 6
RfactorNum. reflection% reflection
Rfree0.2875 132 5.03 %
Rwork0.1981 2493 -
all0.2027 2625 -
obs--99.75 %

+
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