[English] 日本語
Yorodumi
- PDB-7d36: Crystal Structure of BACE1 in complex with N-{3-[(3S)-1-amino-5-f... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 7d36
TitleCrystal Structure of BACE1 in complex with N-{3-[(3S)-1-amino-5-fluoro-3-methyl-3,4-dihydro-2,6-naphthyridin-3-yl]-4-fluorophenyl}-5-cyano-3-methylpyridine-2-carboxamide
ComponentsBeta-secretase 1
KeywordsHYDROLASE / BACE1
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. / Aspartic peptidase, active site / Eukaryotic and viral aspartyl proteases active site. / Aspartic peptidase domain superfamily
Similarity search - Domain/homology
Chem-GUC / IODIDE ION / Beta-secretase 1
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / MOLECULAR REPLACEMENT / molecular replacement / Resolution: 2.3 Å
AuthorsNakahara, K. / Mitsuoka, Y. / Kasuya, S. / Yamamoto, T. / Yamamoto, S. / Ito, H. / Kido, Y. / Kusakabe, K.I.
CitationJournal: Eur.J.Med.Chem. / Year: 2021
Title: Balancing potency and basicity by incorporating fluoropyridine moieties: Discovery of a 1-amino-3,4-dihydro-2,6-naphthyridine BACE1 inhibitor that affords robust and sustained central A beta reduction.
Authors: Nakahara, K. / Mitsuoka, Y. / Kasuya, S. / Yamamoto, T. / Yamamoto, S. / Ito, H. / Kido, Y. / Kusakabe, K.I.
History
DepositionSep 18, 2020Deposition site: PDBJ / Processing site: PDBJ
Revision 1.0Jul 28, 2021Provider: repository / Type: Initial release
Revision 1.1Nov 29, 2023Group: 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)47,6099
Polymers46,3931
Non-polymers1,2168
Water3,099172
1


  • Idetical with deposited unit
  • defined by author
  • Evidence: assay for oligomerization
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area1260 Å2
ΔGint0 kcal/mol
Surface area15630 Å2
Unit cell
Length a, b, c (Å)102.531, 102.531, 170.115
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 / 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: 46393.043 Da / Num. of mol.: 1
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.: 4 / Source method: obtained synthetically / Formula: I
#3: Chemical ChemComp-GOL / GLYCEROL / GLYCERIN / PROPANE-1,2,3-TRIOL


Mass: 92.094 Da / Num. of mol.: 3 / Source method: obtained synthetically / Formula: C3H8O3
#4: Chemical ChemComp-GUC / N-[3-[(3S)-1-azanyl-5-fluoranyl-3-methyl-4H-2,6-naphthyridin-3-yl]-4-fluoranyl-phenyl]-5-cyano-3-methyl-pyridine-2-carboxamide


Mass: 432.425 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C23H18F2N6O / Feature type: SUBJECT OF INVESTIGATION
#5: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 172 / 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: 2.78 Å3/Da / Density % sol: 55.79 %
Crystal growTemperature: 293 K / Method: vapor diffusion, sitting drop / pH: 6.5
Details: 0.2 M sodium citrate tribasic pH 6.5, 0.2 M ammonium iodide, 18.6% w/v PEG 5000MME

-
Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: ROTATING ANODE / Type: RIGAKU MICROMAX-007 HF / Wavelength: 1.54178 Å
DetectorType: RIGAKU RAXIS IV++ / Detector: IMAGE PLATE / Date: Apr 17, 2013
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1.54178 Å / Relative weight: 1
ReflectionResolution: 2.3→50 Å / Num. obs: 24130 / % possible obs: 99.5 % / Redundancy: 8.3 % / Rmerge(I) obs: 0.094 / Χ2: 1.062 / Net I/σ(I): 8.9 / Num. measured all: 199629
Reflection shell
Resolution (Å)Redundancy (%)Rmerge(I) obsNum. unique obsΧ2Diffraction-ID% possible all
2.3-2.348.40.5211890.73199.3
2.34-2.388.50.47711510.732199.4
2.38-2.438.40.47311770.762199.2
2.43-2.488.40.39311660.747199.3
2.48-2.538.50.3711780.756199.7
2.53-2.598.40.31311910.794199.3
2.59-2.668.40.28611740.808199.7
2.66-2.738.40.26511850.836199.6
2.73-2.818.40.23111900.812199.7
2.81-2.98.40.19111930.896199.8
2.9-38.40.15512030.966199.8
3-3.128.40.1311981.041199.8
3.12-3.268.40.10912001.064199.9
3.26-3.448.30.09712161.1881100
3.44-3.658.30.07212181.31100
3.65-3.938.20.06112191.4611100
3.93-4.338.20.05312331.46199.7
4.33-4.958.10.04412411.477199.6
4.95-6.2480.04912591.518199.3
6.24-507.30.04113491.902196.4

-
Phasing

PhasingMethod: molecular replacement
Phasing MR
Highest resolutionLowest resolution
Rotation3 Å47.79 Å
Translation47.79 Å3 Å

-
Processing

Software
NameVersionClassificationNB
HKL-2000data reduction
HKL-2000data scaling
MOLREPphasing
REFMAC5.5.0102refinement
PDB_EXTRACT3.25data extraction
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 1W50

1w50


Resolution: 2.3→20 Å / Cor.coef. Fo:Fc: 0.934 / Cor.coef. Fo:Fc free: 0.901 / SU B: 6.533 / SU ML: 0.161 / SU R Cruickshank DPI: 0.2976 / Cross valid method: THROUGHOUT / σ(F): 0 / ESU R: 0.298 / ESU R Free: 0.241 / Stereochemistry target values: MAXIMUM LIKELIHOOD
Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS U VALUES : REFINED INDIVIDUALLY
RfactorNum. reflection% reflectionSelection details
Rfree0.2652 2437 10.1 %RANDOM
Rwork0.2129 ---
obs0.2181 21623 99.67 %-
Solvent computationIon probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å / Solvent model: BABINET MODEL WITH MASK
Displacement parametersBiso max: 86.45 Å2 / Biso mean: 44.425 Å2 / Biso min: 23.72 Å2
Baniso -1Baniso -2Baniso -3
1-0.01 Å20.01 Å20 Å2
2--0.01 Å20 Å2
3----0.02 Å2
Refinement stepCycle: final / Resolution: 2.3→20 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms2902 0 54 172 3128
Biso mean--55.47 45.27 -
Num. residues----378
Refine LS restraints
Refine-IDTypeDev idealDev ideal targetNumber
X-RAY DIFFRACTIONr_bond_refined_d0.0110.0223030
X-RAY DIFFRACTIONr_angle_refined_deg1.3631.964125
X-RAY DIFFRACTIONr_dihedral_angle_1_deg6.7415376
X-RAY DIFFRACTIONr_dihedral_angle_2_deg34.16223.385130
X-RAY DIFFRACTIONr_dihedral_angle_3_deg15.29915445
X-RAY DIFFRACTIONr_dihedral_angle_4_deg14.8781517
X-RAY DIFFRACTIONr_chiral_restr0.0870.2444
X-RAY DIFFRACTIONr_gen_planes_refined0.0050.0212337
LS refinement shellResolution: 2.3→2.359 Å / Rfactor Rfree error: 0 / Total num. of bins used: 20
RfactorNum. reflection% reflection
Rfree0.278 174 -
Rwork0.237 1541 -
all-1715 -
obs--99.42 %

+
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