[English] 日本語
Yorodumi
- PDB-6wny: Crystal structure of BACE1 in complex with (Z)-fluoro-olefin cont... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 6wny
TitleCrystal structure of BACE1 in complex with (Z)-fluoro-olefin containing compound 15
ComponentsBeta-secretase 1
KeywordsHYDROLASE/HYDROLASE Inhibitor / aspartic protease / amyloid precursor protein / APP / Alzheimer's disease / 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 / 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 / synaptic vesicle / late endosome / 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
IODIDE ION / Chem-U64 / Beta-secretase 1
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.86 Å
AuthorsWhittington, D.A.
Citation
Journal: Bioorg.Med.Chem.Lett. / Year: 2020
Title: The development of a structurally distinct series of BACE1 inhibitors via the (Z)-fluoro-olefin amide bioisosteric replacement.
Authors: Frohn, M. / Liu, L. / Siegmund, A.C. / Qian, W. / Amegadzie, A. / Chen, N. / Tan, H. / Hickman, D. / Wood, S. / Wen, P.H. / Bartberger, M.D. / Whittington, D.A. / Allen, J.R. / Bourbeau, M.P.
#1: Journal: Bioorg.Med.Chem.Lett. / Year: 2020
Title: The development of a structurally distinct series of BACE1 inhibitors via the (Z)-fluoro-olefin amide bioisosteric replacement
Authors: Frohn, M. / Liu, L. / Siegmund, A.C. / Qian, W. / Amegadzie, A. / Chen, N. / Tan, H. / Hickman, D. / Wood, S. / Wen, P.H. / Bartberger, M.D. / Whittington, D.A. / Allen, J.R. / Bourbeau, M.P.
History
DepositionApr 23, 2020Deposition site: RCSB / Processing site: RCSB
Revision 1.0Jun 3, 2020Provider: repository / Type: Initial release
Revision 1.1Jun 24, 2020Group: Database references / Category: citation / citation_author
Revision 1.2Apr 3, 2024Group: Data collection / Database references / Refinement description
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / database_2 / pdbx_initial_refinement_model
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
hetero molecules


Theoretical massNumber of molelcules
Total (without water)46,6995
Polymers45,8221
Non-polymers8764
Water7,530418
1


  • Idetical with deposited unit
  • defined by author&software
  • Evidence: gel filtration
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
Unit cell
Length a, b, c (Å)101.783, 101.783, 171.141
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-504-

IOD

21A-619-

HOH

31A-694-

HOH

41A-855-

HOH

51A-989-

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: 45822.445 Da / Num. of mol.: 1 / 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-U64 / 6-[(Z)-2-{3-[(1S,5S,6S)-3-amino-5-methyl-1-(morpholine-4-carbonyl)-2-thia-4-azabicyclo[4.1.0]hept-3-en-5-yl]-4-fluorophenyl}-1-fluoroethenyl]pyridine-3-carbonitrile


Mass: 495.544 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C25H23F2N5O2S / Feature type: SUBJECT OF INVESTIGATION
#3: Chemical ChemComp-IOD / IODIDE ION


Mass: 126.904 Da / Num. of mol.: 3 / Source method: obtained synthetically / Formula: I
#4: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 418 / Source method: isolated from a natural source / Formula: H2O
Has ligand of interestY

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 2.79 Å3/Da / Density % sol: 55.95 %
Crystal growTemperature: 293 K / Method: vapor diffusion, hanging drop / pH: 6.6
Details: 21% PEG 5000 MME, 190 mM ammonium iodide, 190 mM sodium citrate, 3% (v/v) DMSO

-
Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: APS / Beamline: 22-ID / Wavelength: 0.99 Å
DetectorType: RAYONIX MX-300 / Detector: CCD / Date: Apr 13, 2016
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.99 Å / Relative weight: 1
ReflectionResolution: 1.86→50 Å / Num. obs: 44381 / % possible obs: 99.1 % / Observed criterion σ(I): -3 / Redundancy: 7.1 % / Biso Wilson estimate: 19.23 Å2 / Rmerge(I) obs: 0.066 / Rpim(I) all: 0.026 / Rrim(I) all: 0.071 / Χ2: 0.913 / Net I/σ(I): 8.3
Reflection shell

Diffraction-ID: 1

Resolution (Å)Redundancy (%)Rmerge(I) obsNum. unique obsCC1/2Rpim(I) allRrim(I) allΧ2% possible all
1.86-1.936.70.91343540.7040.3770.990.83399.9
1.93-270.61643800.8640.2470.6650.87599.9
2-2.0970.43143910.920.1730.4660.95299.8
2.09-2.2170.30143950.960.1210.3251.00599.8
2.21-2.347.10.22144090.9730.0880.2381.04699.6
2.34-2.527.20.16444040.9860.0650.1771.00299.5
2.52-2.787.30.10944260.9910.0430.1170.98499.2
2.78-3.187.30.06444600.9970.0250.0690.89398.9
3.18-4.017.20.04644850.9980.0180.051.02398.5
4.01-506.90.02746770.9980.0110.030.52196.5

-
Processing

Software
NameVersionClassification
HKL-2000data scaling
PHENIX1.10.1_2155refinement
PDB_EXTRACT3.25data extraction
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: proprietary structure

Resolution: 1.86→34.9 Å / SU ML: 0.2 / Cross valid method: THROUGHOUT / σ(F): 1.34 / Phase error: 19.41
RfactorNum. reflection% reflection
Rfree0.2094 1996 4.55 %
Rwork0.1675 --
obs0.1693 43840 98.11 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å
Displacement parametersBiso max: 110.6 Å2 / Biso mean: 27.4 Å2 / Biso min: 7.51 Å2
Refinement stepCycle: final / Resolution: 1.86→34.9 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms2973 0 38 418 3429
Biso mean--19.93 34.27 -
Num. residues----380
Refine LS restraints
Refine-IDTypeDev idealNumber
X-RAY DIFFRACTIONf_bond_d0.0113091
X-RAY DIFFRACTIONf_angle_d1.0364211
X-RAY DIFFRACTIONf_chiral_restr0.06457
X-RAY DIFFRACTIONf_plane_restr0.007539
X-RAY DIFFRACTIONf_dihedral_angle_d14.3321798
LS refinement shell

Refine-ID: X-RAY DIFFRACTION / Rfactor Rfree error: 0

Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection Rwork% reflection obs (%)
1.86-1.90590.29581290.2397248485
1.9059-1.95740.27061430.2231296798
1.9574-2.0150.24311410.20772970100
2.015-2.080.21781400.19112993100
2.08-2.15440.23181280.17593014100
2.1544-2.24060.19941310.16842998100
2.2406-2.34260.2311460.16533009100
2.3426-2.46610.19841540.16732989100
2.4661-2.62050.28071610.16613005100
2.6205-2.82280.22381540.1727301099
2.8228-3.10670.20151490.1668302399
3.1067-3.55580.20481370.1588306299
3.5558-4.47850.17251470.1354308498
4.4785-34.8770.17331360.1649323697

+
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