[English] 日本語
Yorodumi
- PDB-4i0h: SPR and structural analysis yield insight towards mechanism of in... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 4i0h
TitleSPR and structural analysis yield insight towards mechanism of inhibition of BACE inhibitors.
ComponentsBeta-secretase 1
Keywordshydrolase/hydrolase inhibitor / BACE / Asp protease / hydrolysis / 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 / amyloid-beta metabolic process ...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 / amyloid-beta metabolic process / detection of mechanical stimulus involved in sensory perception of pain / 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 / dendrite / neuronal cell body / 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-1BL / Beta-secretase 1
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / MOLECULAR REPLACEMENT / Resolution: 2.2 Å
AuthorsYao, N. / Brecht, E.
CitationJournal: To be Published
Title: SPR and structural analysis yield insight towards mechanism of inhibition of BACE inhibitors
Authors: Mondal, K. / Regnstrom, K. / Morishige, W. / Barbour, R. / Beroza, P. / Yao, N. / Bova, M.P.
History
DepositionNov 16, 2012Deposition site: RCSB / Processing site: RCSB
Revision 1.0Mar 6, 2013Provider: repository / Type: Initial release

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Beta-secretase 1
B: Beta-secretase 1
C: Beta-secretase 1
hetero molecules


Theoretical massNumber of molelcules
Total (without water)138,0176
Polymers136,3353
Non-polymers1,6823
Water5,386299
1
A: Beta-secretase 1
hetero molecules


Theoretical massNumber of molelcules
Total (without water)46,0062
Polymers45,4451
Non-polymers5611
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
2
B: Beta-secretase 1
hetero molecules


Theoretical massNumber of molelcules
Total (without water)46,0062
Polymers45,4451
Non-polymers5611
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
3
C: Beta-secretase 1
hetero molecules


Theoretical massNumber of molelcules
Total (without water)46,0062
Polymers45,4451
Non-polymers5611
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
Unit cell
Length a, b, c (Å)83.201, 105.467, 100.265
Angle α, β, γ (deg.)90.00, 105.11, 90.00
Int Tables number4
Space group name H-MP1211
Noncrystallographic symmetry (NCS)NCS domain:
IDEns-IDDetails
11A
21B
31C

-
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: 45445.121 Da / Num. of mol.: 3
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-1BL / (2R)-5-{[(2S,3R)-4-{[1-(3-tert-butylphenyl)cyclohexyl]amino}-1-(3,5-difluorophenyl)-3-hydroxybutan-2-yl]amino}-2-hydroxy-5-oxopentanoic acid


Mass: 560.672 Da / Num. of mol.: 3 / Source method: obtained synthetically / Formula: C31H42F2N2O5
#3: Water ChemComp-HOH / water / Water


Mass: 18.015 Da / Num. of mol.: 299 / 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: 3.12 Å3/Da / Density % sol: 60.51 %
Crystal growTemperature: 291 K / Method: vapor diffusion, sitting drop / pH: 5.3
Details: Human BACE protein containing residues 57-453 and a C-terminal 6His-tag was concentrated to 6mg/ml in buffer 0.1M borate pH 8.5. Compound was added to give a final molar access of compound: ...Details: Human BACE protein containing residues 57-453 and a C-terminal 6His-tag was concentrated to 6mg/ml in buffer 0.1M borate pH 8.5. Compound was added to give a final molar access of compound:protein of 8:1. Protein and compound were then incubated on ice for 1 hour. The drops were set up with a 1:1(v/v) ratio of protein to mother liquor in a total volume of 2 ul. Diffraction quality crystals of BACE in complex with compound was obtained by sitting-drop vapor diffusion method at 291K against a reservoir containing 0.1 M sodium acetate, 2% PEG8000, VAPOR DIFFUSION, SITTING DROP

-
Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: ROTATING ANODE / Type: RIGAKU MICROMAX-007 HF / Wavelength: 1.5418 Å
DetectorType: RIGAKU RAXIS HTC / Detector: IMAGE PLATE / Date: Jan 1, 2010
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1.5418 Å / Relative weight: 1
ReflectionResolution: 2→60 Å / Num. all: 84800 / Num. obs: 87435 / % possible obs: 97 % / Observed criterion σ(F): 1 / Observed criterion σ(I): 1

-
Processing

Software
NameVersionClassification
CrystalCleardata collection
MOLREPphasing
REFMAC5.5.0102refinement
CrystalCleardata reduction
CrystalCleardata scaling
RefinementMethod to determine structure: MOLECULAR REPLACEMENT / Resolution: 2.2→60 Å / Cor.coef. Fo:Fc: 0.953 / Cor.coef. Fo:Fc free: 0.933 / SU B: 7.136 / SU ML: 0.175 / Cross valid method: THROUGHOUT / ESU R: 0.226 / ESU R Free: 0.204 / Stereochemistry target values: MAXIMUM LIKELIHOOD
RfactorNum. reflection% reflectionSelection details
Rfree0.2667 4201 5 %RANDOM
Rwork0.21703 ---
obs0.21961 79824 99.09 %-
Solvent computationIon probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.4 Å / Solvent model: BABINET MODEL WITH MASK
Displacement parametersBiso mean: 67.888 Å2
Baniso -1Baniso -2Baniso -3
1--0.5 Å20 Å2-1.43 Å2
2--1.5 Å20 Å2
3----1.75 Å2
Refinement stepCycle: LAST / Resolution: 2.2→60 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms8833 0 120 299 9252
Refine LS restraints
Refine-IDTypeDev idealDev ideal targetNumber
X-RAY DIFFRACTIONr_bond_refined_d0.0220.0229194
X-RAY DIFFRACTIONr_bond_other_d
X-RAY DIFFRACTIONr_angle_refined_deg2.0191.96112504
X-RAY DIFFRACTIONr_angle_other_deg
X-RAY DIFFRACTIONr_dihedral_angle_1_deg8.10751114
X-RAY DIFFRACTIONr_dihedral_angle_2_deg35.64223.72414
X-RAY DIFFRACTIONr_dihedral_angle_3_deg17.585151439
X-RAY DIFFRACTIONr_dihedral_angle_4_deg20.6531551
X-RAY DIFFRACTIONr_chiral_restr0.1420.21353
X-RAY DIFFRACTIONr_gen_planes_refined0.010.0217038
X-RAY DIFFRACTIONr_gen_planes_other
X-RAY DIFFRACTIONr_nbd_refined
X-RAY DIFFRACTIONr_nbd_other
X-RAY DIFFRACTIONr_nbtor_refined
X-RAY DIFFRACTIONr_nbtor_other
X-RAY DIFFRACTIONr_xyhbond_nbd_refined
X-RAY DIFFRACTIONr_xyhbond_nbd_other
X-RAY DIFFRACTIONr_metal_ion_refined
X-RAY DIFFRACTIONr_metal_ion_other
X-RAY DIFFRACTIONr_symmetry_vdw_refined
X-RAY DIFFRACTIONr_symmetry_vdw_other
X-RAY DIFFRACTIONr_symmetry_hbond_refined
X-RAY DIFFRACTIONr_symmetry_hbond_other
X-RAY DIFFRACTIONr_symmetry_metal_ion_refined
X-RAY DIFFRACTIONr_symmetry_metal_ion_other
X-RAY DIFFRACTIONr_mcbond_it1.1141.55563
X-RAY DIFFRACTIONr_mcbond_other
X-RAY DIFFRACTIONr_mcangle_it2.00728991
X-RAY DIFFRACTIONr_scbond_it2.83433631
X-RAY DIFFRACTIONr_scangle_it4.4284.53513
X-RAY DIFFRACTIONr_rigid_bond_restr
X-RAY DIFFRACTIONr_sphericity_free
X-RAY DIFFRACTIONr_sphericity_bonded
Refine LS restraints NCS

Ens-ID: 1 / Number: 2870 / Refine-ID: X-RAY DIFFRACTION

Dom-IDAuth asym-IDTypeRms dev position (Å)Weight position
1AMEDIUM POSITIONAL0.450.5
2BMEDIUM POSITIONAL0.430.5
3CMEDIUM POSITIONAL0.560.5
1AMEDIUM THERMAL1.172
2BMEDIUM THERMAL1.452
3CMEDIUM THERMAL1.382
LS refinement shellResolution: 2.2→2.257 Å / Total num. of bins used: 20
RfactorNum. reflection% reflection
Rfree0.45 288 -
Rwork0.422 5502 -
obs--93.73 %

+
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