[English] 日本語
Yorodumi
- PDB-4n7e: Crystal structure of the Vps10p domain of human sortilin/NTS3 in ... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 4n7e
TitleCrystal structure of the Vps10p domain of human sortilin/NTS3 in complex with AF38469
ComponentsSortilin
KeywordsSIGNALING PROTEIN / Sortilin / Small molecule ligand / AF38469 / AF40431 / proNGF / Alzheimer's disease / Beta-propeller Asp-box repeat / Vps10p domain / 10CC domain / Receptor Sorting / Membrane
Function / homology
Function and homology information


neurotensin receptor activity, non-G protein-coupled / negative regulation of lipoprotein lipase activity / Golgi to lysosome transport / myotube differentiation / cerebellar climbing fiber to Purkinje cell synapse / plasma membrane to endosome transport / retromer complex binding / maintenance of synapse structure / Golgi to endosome transport / nerve growth factor receptor activity ...neurotensin receptor activity, non-G protein-coupled / negative regulation of lipoprotein lipase activity / Golgi to lysosome transport / myotube differentiation / cerebellar climbing fiber to Purkinje cell synapse / plasma membrane to endosome transport / retromer complex binding / maintenance of synapse structure / Golgi to endosome transport / nerve growth factor receptor activity / vesicle organization / endosome transport via multivesicular body sorting pathway / nerve growth factor binding / protein targeting to lysosome / trans-Golgi network transport vesicle / clathrin-coated vesicle / Golgi cisterna membrane / Golgi Associated Vesicle Biogenesis / negative regulation of fat cell differentiation / endosome to lysosome transport / glucose import / neurotrophin TRK receptor signaling pathway / extrinsic apoptotic signaling pathway via death domain receptors / neuropeptide signaling pathway / clathrin-coated pit / ossification / response to insulin / endocytosis / cytoplasmic vesicle / regulation of gene expression / nuclear membrane / lysosome / early endosome / endosome membrane / G protein-coupled receptor signaling pathway / lysosomal membrane / endoplasmic reticulum membrane / perinuclear region of cytoplasm / Golgi apparatus / enzyme binding / cell surface / membrane / plasma membrane / cytosol
Similarity search - Function
Sortilin Vps10-D, 10CC-a domain / Wheat Germ Agglutinin (Isolectin 2); domain 1 - #270 / VPS10 / Sortilin, C-terminal / Sortilin, N-terminal / Sortilin, neurotensin receptor 3, C-terminal / Sortilin, neurotensin receptor 3, / VPS10 / Complement Module; domain 1 / Wheat Germ Agglutinin (Isolectin 2); domain 1 ...Sortilin Vps10-D, 10CC-a domain / Wheat Germ Agglutinin (Isolectin 2); domain 1 - #270 / VPS10 / Sortilin, C-terminal / Sortilin, N-terminal / Sortilin, neurotensin receptor 3, C-terminal / Sortilin, neurotensin receptor 3, / VPS10 / Complement Module; domain 1 / Wheat Germ Agglutinin (Isolectin 2); domain 1 / Ribbon / WD40/YVTN repeat-like-containing domain superfamily / 2-Layer Sandwich / Mainly Beta / Alpha Beta
Similarity search - Domain/homology
Chem-2JQ / TRIETHYLENE GLYCOL / Sortilin
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.7 Å
AuthorsAndersen, J.L. / Strandbygaard, D. / Thirup, S.
CitationJournal: Bioorg.Med.Chem.Lett. / Year: 2014
Title: The identification of AF38469: An orally bioavailable inhibitor of the VPS10P family sorting receptor Sortilin.
Authors: Schrder, T.J. / Christensen, S. / Lindberg, S. / Langgard, M. / David, L. / Maltas, P.J. / Eskildsen, J. / Jacobsen, J. / Tagmose, L. / Simonsen, K.B. / Biilmann Rnn, L.C. / de Jong, I.E. / ...Authors: Schrder, T.J. / Christensen, S. / Lindberg, S. / Langgard, M. / David, L. / Maltas, P.J. / Eskildsen, J. / Jacobsen, J. / Tagmose, L. / Simonsen, K.B. / Biilmann Rnn, L.C. / de Jong, I.E. / Malik, I.J. / Karlsson, J.J. / Bundgaard, C. / Egebjerg, J. / Stavenhagen, J.B. / Strandbygard, D. / Thirup, S. / Andersen, J.L. / Uppalanchi, S. / Pervaram, S. / Kasturi, S.P. / Eradi, P. / Sakumudi, D.R. / Watson, S.P.
History
DepositionOct 15, 2013Deposition site: RCSB / Processing site: RCSB
Revision 1.0Jan 22, 2014Provider: repository / Type: Initial release
Revision 2.0Jul 29, 2020Group: Atomic model / Data collection ...Atomic model / Data collection / Database references / Derived calculations / Structure summary
Category: atom_site / chem_comp ...atom_site / chem_comp / entity / pdbx_branch_scheme / pdbx_chem_comp_identifier / pdbx_entity_branch / pdbx_entity_branch_descriptor / pdbx_entity_branch_link / pdbx_entity_branch_list / pdbx_entity_nonpoly / pdbx_nonpoly_scheme / pdbx_struct_assembly_gen / struct_asym / struct_conn / struct_ref_seq_dif / struct_site / struct_site_gen
Item: _atom_site.auth_asym_id / _atom_site.auth_seq_id ..._atom_site.auth_asym_id / _atom_site.auth_seq_id / _atom_site.label_asym_id / _atom_site.label_entity_id / _chem_comp.name / _chem_comp.type / _entity.formula_weight / _entity.pdbx_description / _entity.pdbx_number_of_molecules / _entity.type / _pdbx_struct_assembly_gen.asym_id_list / _struct_conn.pdbx_dist_value / _struct_conn.pdbx_leaving_atom_flag / _struct_conn.pdbx_role / _struct_conn.ptnr1_auth_asym_id / _struct_conn.ptnr1_auth_comp_id / _struct_conn.ptnr1_auth_seq_id / _struct_conn.ptnr1_label_asym_id / _struct_conn.ptnr1_label_atom_id / _struct_conn.ptnr1_label_comp_id / _struct_conn.ptnr1_label_seq_id / _struct_conn.ptnr2_auth_asym_id / _struct_conn.ptnr2_auth_comp_id / _struct_conn.ptnr2_auth_seq_id / _struct_conn.ptnr2_label_asym_id / _struct_conn.ptnr2_label_comp_id / _struct_ref_seq_dif.details
Description: Carbohydrate remediation / Provider: repository / Type: Remediation
Revision 2.1Sep 20, 2023Group: Data collection / Database references ...Data collection / Database references / Refinement description / Structure summary
Category: chem_comp / chem_comp_atom ...chem_comp / chem_comp_atom / chem_comp_bond / database_2 / pdbx_initial_refinement_model
Item: _chem_comp.pdbx_synonyms / _database_2.pdbx_DOI / _database_2.pdbx_database_accession

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Sortilin
hetero molecules


Theoretical massNumber of molelcules
Total (without water)79,2765
Polymers77,7911
Non-polymers1,4854
Water91951
1


  • Idetical with deposited unit
  • defined by author&software
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
Unit cell
Length a, b, c (Å)161.948, 77.402, 111.176
Angle α, β, γ (deg.)90.00, 127.06, 90.00
Int Tables number5
Space group name H-MC121

-
Components

-
Protein , 1 types, 1 molecules A

#1: Protein Sortilin / 100 kDa NT receptor / Glycoprotein 95 / Gp95 / Neurotensin receptor 3 / NT3 / NTR3


Mass: 77790.883 Da / Num. of mol.: 1 / Fragment: UNP residues 78-756 / Mutation: V617M
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: SORT1 / Plasmid: pCEP-pu / Cell (production host): HEK 293F cell / Production host: Homo Sapiens (human) / References: UniProt: Q99523

-
Sugars , 2 types, 2 molecules

#2: Polysaccharide beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta- ...beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose


Type: oligosaccharide / Mass: 586.542 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
DescriptorTypeProgram
DManpb1-4DGlcpNAcb1-4DGlcpNAcb1-Glycam Condensed SequenceGMML 1.0
WURCS=2.0/2,3,2/[a2122h-1b_1-5_2*NCC/3=O][a1122h-1b_1-5]/1-1-2/a4-b1_b4-c1WURCSPDB2Glycan 1.1.0
[]{[(4+1)][b-D-GlcpNAc]{[(4+1)][b-D-GlcpNAc]{[(4+1)][b-D-Manp]{}}}}LINUCSPDB-CARE
#3: Polysaccharide 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose


Type: oligosaccharide / Mass: 424.401 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
DescriptorTypeProgram
DGlcpNAcb1-4DGlcpNAcb1-Glycam Condensed SequenceGMML 1.0
WURCS=2.0/1,2,1/[a2122h-1b_1-5_2*NCC/3=O]/1-1/a4-b1WURCSPDB2Glycan 1.1.0
[]{[(4+1)][b-D-GlcpNAc]{[(4+1)][b-D-GlcpNAc]{}}}LINUCSPDB-CARE

-
Non-polymers , 3 types, 53 molecules

#4: Chemical ChemComp-PGE / TRIETHYLENE GLYCOL / Polyethylene glycol


Mass: 150.173 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C6H14O4
#5: Chemical ChemComp-2JQ / 2-[(6-methylpyridin-2-yl)carbamoyl]-5-(trifluoromethyl)benzoic acid


Mass: 324.255 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C15H11F3N2O3
#6: Water ChemComp-HOH / water / Water


Mass: 18.015 Da / Num. of mol.: 51 / 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: 3.57 Å3/Da / Density % sol: 65.58 %
Crystal growTemperature: 292 K / Method: vapor diffusion, sitting drop / pH: 7.3
Details: 0.1 M HEPES-Tris, 0.4 M sodium malonate, 27 % (w/v) PEG 3350, 4.5 % (v/v) glycerol, pH 7.3, VAPOR DIFFUSION, SITTING DROP, temperature 292K

-
Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: SYNCHROTRON / Site: SLS / Beamline: X06DA / Wavelength: 0.9 Å
DetectorType: DECTRIS PILATUS 2M-F / Detector: PIXEL / Date: May 15, 2012
RadiationMonochromator: Bartels Monochromator / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.9 Å / Relative weight: 1
ReflectionResolution: 2.7→46.7 Å / Num. all: 30397 / Num. obs: 30397 / % possible obs: 99.7 % / Observed criterion σ(F): 1.34 / Observed criterion σ(I): 2 / Redundancy: 6.9 % / Biso Wilson estimate: 84.3 Å2 / Rmerge(I) obs: 0.071 / Rsym value: 0.071 / Net I/σ(I): 15.2
Reflection shell
Resolution (Å)Rmerge(I) obsMean I/σ(I) obsDiffraction-ID% possible all
2.7-2.80.8452.2197.9
2.8-30.5223.71100
3-3.20.2776.21100
3.2-3.50.15810.51100
3.5-3.80.09215.51100
3.8-4.30.06221.51100
4.3-4.90.04530.91100
4.9-60.04630.61100
6-8.50.04431.11100
8.5-46.70.03346199.4

-
Processing

Software
NameVersionClassification
DNAdata collection
PHASERphasing
PHENIX(phenix.refine: 1.8.3_1479)refinement
XDSdata reduction
SCALAdata scaling
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: PDB ENTRY 3F6K with ligand, glycosylations and waters removed

3f6k


Resolution: 2.7→44.4 Å / SU ML: 0.38 / σ(F): 1.34 / Phase error: 28.65 / Stereochemistry target values: ML
RfactorNum. reflection% reflectionSelection details
Rfree0.2416 2223 7.32 %Random
Rwork0.2008 ---
obs0.2038 30366 99.6 %-
all-30397 --
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL
Refinement stepCycle: LAST / Resolution: 2.7→44.4 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms5140 0 100 51 5291
Refine LS restraints
Refine-IDTypeDev idealNumber
X-RAY DIFFRACTIONf_bond_d0.0115367
X-RAY DIFFRACTIONf_angle_d1.3547258
X-RAY DIFFRACTIONf_dihedral_angle_d15.2371942
X-RAY DIFFRACTIONf_chiral_restr0.061793
X-RAY DIFFRACTIONf_plane_restr0.007929
LS refinement shell
Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkRefine-ID% reflection obs (%)
2.7-2.75490.34061300.33691640X-RAY DIFFRACTION95
2.7549-2.8190.321390.30931763X-RAY DIFFRACTION100
2.819-2.88950.34841340.28321783X-RAY DIFFRACTION100
2.8895-2.96760.33261410.27631732X-RAY DIFFRACTION100
2.9676-3.05490.35531400.28111752X-RAY DIFFRACTION100
3.0549-3.15350.32071390.27091754X-RAY DIFFRACTION100
3.1535-3.26620.3171380.25031752X-RAY DIFFRACTION100
3.2662-3.39690.24181400.23521743X-RAY DIFFRACTION100
3.3969-3.55140.23891370.21421759X-RAY DIFFRACTION100
3.5514-3.73860.24911370.21551787X-RAY DIFFRACTION100
3.7386-3.97270.26041350.20371745X-RAY DIFFRACTION100
3.9727-4.27920.21951480.16571778X-RAY DIFFRACTION100
4.2792-4.70940.18511370.15341761X-RAY DIFFRACTION100
4.7094-5.38980.2131420.1611769X-RAY DIFFRACTION100
5.3898-6.78670.23911380.18381790X-RAY DIFFRACTION100
6.7867-44.36430.21471480.18921835X-RAY DIFFRACTION100
Refinement TLS params.

Method: refined / Refine-ID: X-RAY DIFFRACTION

IDL11 (°2)L12 (°2)L13 (°2)L22 (°2)L23 (°2)L33 (°2)S11 (Å °)S12 (Å °)S13 (Å °)S21 (Å °)S22 (Å °)S23 (Å °)S31 (Å °)S32 (Å °)S33 (Å °)T11 (Å2)T12 (Å2)T13 (Å2)T22 (Å2)T23 (Å2)T33 (Å2)Origin x (Å)Origin y (Å)Origin z (Å)
13.091-2.1932-0.65.1885-0.45842.98090.172-0.83840.23060.79590.0649-0.165-0.61420.399-0.16690.8964-0.2521-0.07540.7899-0.10320.5767-17.49436.650639.4273
22.3265-1.0199-0.15827.2941.29413.97810.37410.41380.3582-0.0911-0.29320.329-1.0896-0.593-0.05510.6850.13330.1220.59010.08360.4514-28.296839.66111.1504
33.3568-0.0639-1.29462.2603-0.26765.5782-0.091-0.146-0.63960.4182-0.195-0.07920.68090.11210.22140.4805-0.08070.02520.37950.06260.6396-18.928611.32821.9023
45.2342-2.8021-0.24623.5579-0.02393.02750.69010.969-0.0068-0.6824-0.7077-0.0208-0.1422-0.40260.12420.46650.06710.06770.95130.11520.7826-18.397528.9515-1.876
54.1353-4.02612.75683.9631-2.71151.84140.84331.86470.9171-0.6105-1.3497-0.86970.13590.570.38470.66080.30420.2311.34080.35711.0029-21.983539.0975-12.3725
Refinement TLS group
IDRefine-IDRefine TLS-IDSelection details
1X-RAY DIFFRACTION1(CHAIN A AND RESID 54:228)
2X-RAY DIFFRACTION2(CHAIN A AND RESID 229:386)
3X-RAY DIFFRACTION3(CHAIN A AND RESID 387:612)
4X-RAY DIFFRACTION4(CHAIN A AND RESID 613:681)
5X-RAY DIFFRACTION5(CHAIN A AND RESID 682:715)

+
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