[English] 日本語
Yorodumi
- PDB-3rvi: Structure of Bace-1 (Beta-Secretase) in Complex with 2-((2-Amino-... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 3rvi
TitleStructure of Bace-1 (Beta-Secretase) in Complex with 2-((2-Amino-6-o-tolylquinolin-3-yl)methyl)-N-(cyclohexylmethyl)pentanamide
ComponentsBeta-secretase 1
KeywordsHydrolase/Hydrolase Inhibitor / ASPARTYL PROTEASE / 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
IODIDE ION / Chem-RVI / Beta-secretase 1
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.65 Å
AuthorsSickmier, E.A.
CitationJournal: J.Med.Chem. / Year: 2011
Title: From Fragment Screening to In Vivo Efficacy: Optimization of a Series of 2-Aminoquinolines as Potent Inhibitors of Beta-Site Amyloid Precursor Protein Cleaving Enzyme 1 (BACE1).
Authors: Cheng, Y. / Judd, T.C. / Bartberger, M.D. / Brown, J. / Chen, K. / Fremeau, R.T. / Hickman, D. / Hitchcock, S.A. / Jordan, B. / Li, V. / Lopez, P. / Louie, S.W. / Luo, Y. / Michelsen, K. / ...Authors: Cheng, Y. / Judd, T.C. / Bartberger, M.D. / Brown, J. / Chen, K. / Fremeau, R.T. / Hickman, D. / Hitchcock, S.A. / Jordan, B. / Li, V. / Lopez, P. / Louie, S.W. / Luo, Y. / Michelsen, K. / Nixey, T. / Powers, T.S. / Rattan, C. / Sickmier, E.A. / St Jean, D.J. / Wahl, R.C. / Wen, P.H. / Wood, S.
History
DepositionMay 6, 2011Deposition site: RCSB / Processing site: RCSB
Revision 1.0Aug 31, 2011Provider: repository / Type: Initial release

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Beta-secretase 1
hetero molecules


Theoretical massNumber of molelcules
Total (without water)47,33911
Polymers45,8221
Non-polymers1,51610
Water1,20767
1


  • Idetical with deposited unit
  • defined by author&software
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
Unit cell
Length a, b, c (Å)103.124, 103.124, 170.326
Angle α, β, γ (deg.)90.000, 90.000, 120.000
Int Tables number178
Space group name H-MP6122

-
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: 45822.445 Da / Num. of mol.: 1 / Fragment: UNP residues 43-453 / Mutation: R14K, R15K
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-IOD / IODIDE ION


Mass: 126.904 Da / Num. of mol.: 7 / Source method: obtained synthetically / Formula: I
#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: Chemical ChemComp-RVI / (2R)-2-{[2-amino-6-(2-methylphenyl)quinolin-3-yl]methyl}-N-(cyclohexylmethyl)pentanamide / 2-((2-Amino-6-o-tolylquinolin-3-yl)methyl)-N-(cyclohexylmethyl)pentanamide


Mass: 443.624 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C29H37N3O
#5: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 67 / 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: 2.85 Å3/Da / Density % sol: 56.88 %
Crystal growTemperature: 293 K / Method: vapor diffusion, hanging drop / pH: 6.6
Details: 20% (w/v) PEG 5000 monomethylethyl ether (MME), 200mM sodium citrate (pH 6.6) and 200mM sodium iodide, VAPOR DIFFUSION, HANGING DROP, temperature 293K

-
Data collection

Diffraction sourceSource: SYNCHROTRON / Site: ALS / Beamline: 5.0.2 / Wavelength: 1 Å
DetectorType: ADSC QUANTUM 315 / Detector: CCD / Date: Aug 28, 2008
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1 Å / Relative weight: 1
ReflectionResolution: 2.65→20 Å / Num. obs: 15352 / % possible obs: 94.5 % / Redundancy: 9.8 % / Rmerge(I) obs: 0.09 / Χ2: 1.064 / Net I/σ(I): 9.4
Reflection shell
Resolution (Å)Redundancy (%)Rmerge(I) obsNum. unique allΧ2Diffraction-ID% possible all
2.65-2.749.70.49115101.022196.4
2.74-2.859.80.38215221.031196
2.85-2.989.90.27115211.067195.8
2.98-3.14100.19515141.072195.5
3.14-3.349.90.14115301.09195.1
3.34-3.599.90.09615191.145194.8
3.59-3.959.90.06215231.042194.3
3.95-4.529.90.04815401.036193.7
4.52-5.679.80.04115501.033193
5.67-209.30.04316231.103190.5

-
Processing

Software
NameVersionClassificationNB
SCALEPACKdata scaling
REFMACrefinement
PDB_EXTRACT3.1data extraction
HKL-2000data reduction
PHASERphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT / Resolution: 2.65→20 Å / Cor.coef. Fo:Fc: 0.917 / Cor.coef. Fo:Fc free: 0.887 / WRfactor Rfree: 0.261 / WRfactor Rwork: 0.2207 / Occupancy max: 1 / Occupancy min: 0.25 / FOM work R set: 0.8155 / SU B: 10.54 / SU ML: 0.219 / SU R Cruickshank DPI: 0.6929 / SU Rfree: 0.3288 / Cross valid method: THROUGHOUT / σ(F): 0 / ESU R Free: 0.329 / Stereochemistry target values: MAXIMUM LIKELIHOOD
Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS U VALUES: REFINED INDIVIDUALLY
RfactorNum. reflection% reflectionSelection details
Rfree0.261 763 5 %RANDOM
Rwork0.2208 ---
obs0.2227 15205 94.17 %-
Solvent computationIon probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.4 Å / Solvent model: MASK
Displacement parametersBiso max: 74.07 Å2 / Biso mean: 33.7719 Å2 / Biso min: 3.45 Å2
Baniso -1Baniso -2Baniso -3
1--0.76 Å2-0.38 Å20 Å2
2---0.76 Å20 Å2
3---1.14 Å2
Refinement stepCycle: LAST / Resolution: 2.65→20 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms2910 0 52 67 3029
Refine LS restraints
Refine-IDTypeDev idealDev ideal targetNumber
X-RAY DIFFRACTIONr_bond_refined_d0.0070.0223033
X-RAY DIFFRACTIONr_angle_refined_deg1.0311.9594118
X-RAY DIFFRACTIONr_dihedral_angle_1_deg5.8545366
X-RAY DIFFRACTIONr_dihedral_angle_2_deg35.4423.723137
X-RAY DIFFRACTIONr_dihedral_angle_3_deg16.52315477
X-RAY DIFFRACTIONr_dihedral_angle_4_deg9.7111517
X-RAY DIFFRACTIONr_chiral_restr0.0660.2443
X-RAY DIFFRACTIONr_gen_planes_refined0.0030.0212316
X-RAY DIFFRACTIONr_mcbond_it0.4641.51828
X-RAY DIFFRACTIONr_mcangle_it0.84722956
X-RAY DIFFRACTIONr_scbond_it0.6631205
X-RAY DIFFRACTIONr_scangle_it1.1634.51162
LS refinement shellResolution: 2.65→2.718 Å / Total num. of bins used: 20
RfactorNum. reflection% reflection
Rfree0.402 56 -
Rwork0.317 1043 -
all-1099 -
obs--96.07 %

+
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