[English] 日本語
Yorodumi
- PDB-4h3f: Structure of BACE Bound to 3-(5-((7aR)-2-imino-6-(6-methoxypyridi... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 4h3f
TitleStructure of BACE Bound to 3-(5-((7aR)-2-imino-6-(6-methoxypyridin-2-yl)-3-methyl-4-oxooctahydro-1H-pyrrolo[3,4-d]pyrimidin-7a-yl)thiophen-3-yl)benzonitrile
ComponentsBeta-secretase 1
KeywordsHYDROLASE/HYDROLASE INHIBITOR / BACE1 / Alzheimers / 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 / prepulse inhibition / detection of mechanical stimulus involved in sensory perception of pain ...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 / prepulse inhibition / detection of mechanical stimulus involved in sensory perception of pain / amyloid-beta metabolic process / cellular response to copper ion / hippocampal mossy fiber to CA3 synapse / presynaptic modulation of chemical synaptic transmission / multivesicular body / response to lead ion / trans-Golgi network / protein processing / recycling endosome / cellular response to amyloid-beta / positive regulation of neuron apoptotic process / synaptic vesicle / late endosome / amyloid-beta binding / peptidase activity / endopeptidase activity / amyloid fibril formation / lysosome / aspartic-type endopeptidase activity / early endosome / endosome membrane / endosome / membrane raft / Amyloid fiber formation / axon / endoplasmic reticulum lumen / 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-10O / L(+)-TARTARIC ACID / Beta-secretase 1
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / FOURIER SYNTHESIS / Resolution: 1.7 Å
AuthorsStrickland, C. / Mandal, M.
CitationJournal: J.Med.Chem. / Year: 2012
Title: Design and Validation of Bicyclic Iminopyrimidinones As Beta Amyloid Cleaving Enzyme-1 (BACE1) Inhibitors: Conformational Constraint to Favor a Bioactive Conformation.
Authors: Mandal, M. / Zhu, Z. / Cumming, J.N. / Liu, X. / Strickland, C. / Mazzola, R.D. / Caldwell, J.P. / Leach, P. / Grzelak, M. / Hyde, L. / Zhang, Q. / Terracina, G. / Zhang, L. / Chen, X. / ...Authors: Mandal, M. / Zhu, Z. / Cumming, J.N. / Liu, X. / Strickland, C. / Mazzola, R.D. / Caldwell, J.P. / Leach, P. / Grzelak, M. / Hyde, L. / Zhang, Q. / Terracina, G. / Zhang, L. / Chen, X. / Kuvelkar, R. / Kennedy, M.E. / Favreau, L. / Cox, K. / Orth, P. / Buevich, A. / Voigt, J. / Wang, H. / Kazakevich, I. / McKittrick, B.A. / Greenlee, W. / Parker, E.M. / Stamford, A.W.
History
DepositionSep 13, 2012Deposition site: RCSB / Processing site: RCSB
Revision 1.0Nov 7, 2012Provider: repository / Type: Initial release
Revision 1.1Nov 21, 2012Group: Database references

-
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)93,8677
Polymers92,5002
Non-polymers1,3675
Water15,979887
1
A: Beta-secretase 1
hetero molecules


Theoretical massNumber of molelcules
Total (without water)46,8593
Polymers46,2501
Non-polymers6092
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
2
B: Beta-secretase 1
hetero molecules


Theoretical massNumber of molelcules
Total (without water)47,0094
Polymers46,2501
Non-polymers7593
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
Unit cell
Length a, b, c (Å)86.446, 89.215, 131.034
Angle α, β, γ (deg.)90.000, 90.000, 90.000
Int Tables number19
Space group name H-MP212121

-
Components

#1: Protein Beta-secretase 1 / / Aspartyl protease 2 / ASP2 / Asp 2 / Beta-site amyloid precursor protein cleaving enzyme 1 / Beta- ...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: 46249.926 Da / Num. of mol.: 2 / Fragment: UNP Residues 41-454
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: BACE, BACE1, KIAA1149 / Production host: Escherichia coli (E. coli) / Strain (production host): BL21(DE3) / References: UniProt: P56817, memapsin 2
#2: Chemical ChemComp-TLA / L(+)-TARTARIC ACID / Tartaric acid


Mass: 150.087 Da / Num. of mol.: 3 / Source method: obtained synthetically / Formula: C4H6O6
#3: Chemical ChemComp-10O / 3-{5-[(2E,4aR,7aR)-2-imino-6-(6-methoxypyridin-2-yl)-3-methyl-4-oxooctahydro-7aH-pyrrolo[3,4-d]pyrimidin-7a-yl]thiophen-3-yl}benzonitrile


Mass: 458.535 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C24H22N6O2S
#4: Water ChemComp-HOH / water / Water


Mass: 18.015 Da / Num. of mol.: 887 / 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: 2.73 Å3/Da / Density % sol: 54.97 %
Crystal growTemperature: 277 K / Method: vapor diffusion, hanging drop / Details: VAPOR DIFFUSION, HANGING DROP, temperature 277K

-
Data collection

DiffractionMean temperature: 95 K
Diffraction sourceSource: ROTATING ANODE / Type: RIGAKU RU200 / Wavelength: 1.54178 Å
DetectorType: RIGAKU RAXIS IV / Detector: IMAGE PLATE / Date: Apr 17, 2006
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1.54178 Å / Relative weight: 1
ReflectionResolution: 1.7→20 Å / Num. all: 111855 / Num. obs: 106993 / % possible obs: 95.7 % / Observed criterion σ(F): 0 / Observed criterion σ(I): 0 / Redundancy: 2.4 % / Rmerge(I) obs: 0.065 / Χ2: 1 / Net I/σ(I): 10.7
Reflection shell
Resolution (Å)Redundancy (%)Rmerge(I) obsNum. unique allΧ2Diffraction-ID% possible all
1.7-1.732.10.49753541197.1
1.73-1.762.20.41155021.002199.3
1.76-1.792.20.37554801.004199.5
1.79-1.832.20.31655231.003199.4
1.83-1.872.30.2854831199.2
1.87-1.912.30.23754651198.8
1.91-1.962.30.19854751198.4
1.96-2.022.30.16354321197.9
2.02-2.072.30.14653911197.2
2.07-2.142.40.13153711196.7
2.14-2.222.40.11453521196
2.22-2.312.40.10153101195.5
2.31-2.412.40.09653101195.2
2.41-2.542.50.08752631194.5
2.54-2.72.50.07452821193.9
2.7-2.92.50.06252131193.1
2.9-3.22.50.05252231192.4
3.2-3.662.50.0451941192
3.66-4.62.60.03452031190.9
4.6-202.60.0351670.999187.1

-
Processing

Software
NameVersionClassificationNB
SCALEPACKdata scaling
CNSrefinement
PDB_EXTRACT3.11data extraction
CrystalCleardata collection
DENZOdata reduction
CNSphasing
RefinementMethod to determine structure: FOURIER SYNTHESIS / Resolution: 1.7→20 Å / Occupancy max: 1 / Occupancy min: 1 / σ(F): 0
RfactorNum. reflection% reflection
Rfree0.23 5280 4.7 %
Rwork0.1993 --
all-111855 -
obs-106230 95 %
Displacement parametersBiso max: 73.86 Å2 / Biso mean: 21.1717 Å2 / Biso min: 6.61 Å2
Baniso -1Baniso -2Baniso -3
1-2.797 Å20 Å20 Å2
2---3.847 Å20 Å2
3---1.049 Å2
Refinement stepCycle: LAST / Resolution: 1.7→20 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms6112 0 96 887 7095
Refine LS restraints
Refine-IDTypeDev ideal
X-RAY DIFFRACTIONc_bond_d0.006
X-RAY DIFFRACTIONc_angle_d1.488
Xplor file
Refine-IDSerial noParam fileTopol file
X-RAY DIFFRACTION1MSI_CNX_TOPPAR:protein_rep.paramMSI_CNX_TOPPAR:protein.top
X-RAY DIFFRACTION2MSI_CNX_TOPPAR:water_rep.paramMSI_CNX_TOPPAR:water.top
X-RAY DIFFRACTION3MSI_CNX_TOPPAR:ion.paramMSI_CNX_TOPPAR:ion.top
X-RAY DIFFRACTION4paratartrate.protoptartrate.pro
X-RAY DIFFRACTION5parainh.protopinh.pro

+
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