[English] 日本語
Yorodumi
- PDB-6npt: TRK-A IN COMPLEX WITH LIGAND 1 -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 6npt
TitleTRK-A IN COMPLEX WITH LIGAND 1
ComponentsHigh affinity nerve growth factor receptor
KeywordsTRANSFERASE / TRK-A KINASE DOMAIN HIGH AFFINITY NERVE GROWTH FACTOR RECEPTOR Inhibitor
Function / homology
Function and homology information


behavioral response to formalin induced pain / neurotrophin p75 receptor binding / olfactory nerve development / response to hydrostatic pressure / TRKA activation by NGF / PLC-gamma1 signalling / Signalling to STAT3 / programmed cell death involved in cell development / mechanoreceptor differentiation / neurotrophin receptor activity ...behavioral response to formalin induced pain / neurotrophin p75 receptor binding / olfactory nerve development / response to hydrostatic pressure / TRKA activation by NGF / PLC-gamma1 signalling / Signalling to STAT3 / programmed cell death involved in cell development / mechanoreceptor differentiation / neurotrophin receptor activity / nerve growth factor receptor activity / neurotrophin binding / Sertoli cell development / GPI-linked ephrin receptor activity / nerve growth factor signaling pathway / axonogenesis involved in innervation / Retrograde neurotrophin signalling / nerve growth factor binding / NGF-independant TRKA activation / sympathetic nervous system development / Signalling to p38 via RIT and RIN / ARMS-mediated activation / positive regulation of Ras protein signal transduction / positive regulation of programmed cell death / positive regulation of synapse assembly / PI3K/AKT activation / Frs2-mediated activation / detection of temperature stimulus involved in sensory perception of pain / neurotrophin TRK receptor signaling pathway / neuron development / Signalling to RAS / response to axon injury / detection of mechanical stimulus involved in sensory perception of pain / response to electrical stimulus / peptidyl-tyrosine autophosphorylation / transmembrane receptor protein tyrosine kinase activity / B cell differentiation / positive regulation of synaptic transmission, glutamatergic / positive regulation of GTPase activity / response to nutrient levels / cellular response to nerve growth factor stimulus / axon guidance / receptor protein-tyrosine kinase / kinase binding / positive regulation of neuron projection development / peptidyl-tyrosine phosphorylation / cellular response to nicotine / circadian rhythm / recycling endosome membrane / positive regulation of angiogenesis / neuron projection development / late endosome / late endosome membrane / positive regulation of NF-kappaB transcription factor activity / early endosome membrane / protein tyrosine kinase activity / neuron apoptotic process / negative regulation of neuron apoptotic process / protein autophosphorylation / positive regulation of ERK1 and ERK2 cascade / early endosome / positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction / learning or memory / receptor complex / endosome membrane / response to xenobiotic stimulus / positive regulation of protein phosphorylation / protein phosphorylation / negative regulation of cell population proliferation / axon / neuronal cell body / dendrite / negative regulation of apoptotic process / cell surface / protein homodimerization activity / protein-containing complex / ATP binding / identical protein binding / plasma membrane
Similarity search - Function
High affinity nerve growth factor receptor NTRK1 / Tyrosine kinase receptor A, transmembrane domain / Tyrosine kinase receptor A trans-membrane domain / Growth factor receptor NTRK / Growth factor receptor NTRK, leucine rich repeat C-terminal / Leucine rich repeat C-terminal motif / Cysteine-rich flanking region, C-terminal / Leucine rich repeat C-terminal domain / Tyrosine-protein kinase, receptor class II, conserved site / Receptor tyrosine kinase class II signature. ...High affinity nerve growth factor receptor NTRK1 / Tyrosine kinase receptor A, transmembrane domain / Tyrosine kinase receptor A trans-membrane domain / Growth factor receptor NTRK / Growth factor receptor NTRK, leucine rich repeat C-terminal / Leucine rich repeat C-terminal motif / Cysteine-rich flanking region, C-terminal / Leucine rich repeat C-terminal domain / Tyrosine-protein kinase, receptor class II, conserved site / Receptor tyrosine kinase class II signature. / Leucine rich repeat / : / Leucine-rich repeat / Leucine-rich repeat domain superfamily / Tyrosine-protein kinase, catalytic domain / Tyrosine kinase, catalytic domain / Tyrosine protein kinases specific active-site signature. / Tyrosine-protein kinase, active site / Serine-threonine/tyrosine-protein kinase, catalytic domain / Protein tyrosine and serine/threonine kinase / Transferase(Phosphotransferase) domain 1 / Transferase(Phosphotransferase); domain 1 / Phosphorylase Kinase; domain 1 / Phosphorylase Kinase; domain 1 / Ig-like domain profile. / Immunoglobulin-like domain / Immunoglobulin-like domain superfamily / Protein kinase, ATP binding site / Protein kinases ATP-binding region signature. / Immunoglobulin-like fold / Protein kinase domain profile. / Protein kinase domain / Protein kinase-like domain superfamily / 2-Layer Sandwich / Orthogonal Bundle / Mainly Alpha / Alpha Beta
Similarity search - Domain/homology
Chem-KWY / High affinity nerve growth factor receptor
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / Resolution: 2.19 Å
AuthorsSubramanian, G.
CitationJournal: Acs Chem.Biol. / Year: 2019
Title: Deciphering the Allosteric Binding Mechanism of the Human Tropomyosin Receptor Kinase A ( hTrkA) Inhibitors.
Authors: Subramanian, G. / Johnson, P.D. / Zachary, T. / Roush, N. / Zhu, Y. / Bowen, S.J. / Janssen, A. / Duclos, B.A. / Williams, T. / Javens, C. / Shalaly, N.D. / Molina, D.M. / Wittwer, A.J. / Hirsch, J.L.
History
DepositionJan 18, 2019Deposition site: RCSB / Processing site: RCSB
Revision 1.0May 22, 2019Provider: repository / Type: Initial release
Revision 1.1Jul 10, 2019Group: Data collection / Database references / Category: citation / citation_author
Item: _citation.journal_volume / _citation.page_first ..._citation.journal_volume / _citation.page_first / _citation.page_last / _citation.title / _citation_author.name

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: High affinity nerve growth factor receptor
hetero molecules


Theoretical massNumber of molelcules
Total (without water)35,2182
Polymers34,8221
Non-polymers3951
Water1,31573
1


  • Idetical with deposited unit
  • defined by author&software
  • Evidence: surface plasmon resonance
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
Unit cell
Length a, b, c (Å)52.084, 52.084, 225.611
Angle α, β, γ (deg.)90.00, 90.00, 120.00
Int Tables number151
Space group name H-MP3112

-
Components

#1: Protein High affinity nerve growth factor receptor / Neurotrophic tyrosine kinase receptor type 1 / TRK1-transforming tyrosine kinase protein / ...Neurotrophic tyrosine kinase receptor type 1 / TRK1-transforming tyrosine kinase protein / Tropomyosin-related kinase A / Tyrosine kinase receptor / Tyrosine kinase receptor A / Trk-A / gp140trk / p140-TrkA


Mass: 34822.027 Da / Num. of mol.: 1 / Fragment: KINASE DOMAIN
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: NTRK1, MTC, TRK, TRKA / Production host: Spodoptera frugiperda (fall armyworm)
References: UniProt: P04629, receptor protein-tyrosine kinase
#2: Chemical ChemComp-KWY / 4-tert-butyl-N-(1,3-diphenyl-1H-pyrazol-5-yl)benzamide


Mass: 395.496 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C26H25N3O
#3: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 73 / 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: 2.57 Å3/Da / Density % sol: 52.25 %
Crystal growTemperature: 277.15 K / Method: vapor diffusion, hanging drop
Details: The protein at a concentration of 10 mg/ml was mixed with 2mM of the ligand (diluted from 100 mM DMSO stock solution) for 1 hour on ice and crystallized at 4 deg C (hanging drop) from: 0.10 ...Details: The protein at a concentration of 10 mg/ml was mixed with 2mM of the ligand (diluted from 100 mM DMSO stock solution) for 1 hour on ice and crystallized at 4 deg C (hanging drop) from: 0.10 M KH2PO4/ 0.10 M NaH2PO4/ 0.10 M MES/NaOH pH 6.00 and 1.90 M NaCl (cryo: 25% glycerol in reservoir), or 18.00 % (w/v) PEG 3350, 0.20 M CaCl2, 0.10 M, MES pH=6.50 (cryo: direct).

-
Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: SLS / Beamline: X06SA / Wavelength: 1 Å
DetectorType: DECTRIS EIGER X 16M / Detector: PIXEL / Date: Dec 14, 2015
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1 Å / Relative weight: 1
ReflectionResolution: 2.19→75.2 Å / Num. obs: 18386 / % possible obs: 99.1 % / Observed criterion σ(I): 0 / Redundancy: 4.1 % / Rmerge(I) obs: 0.038 / Net I/σ(I): 21.78
Reflection shellResolution: 2.19→2.44 Å / Redundancy: 4 % / Rmerge(I) obs: 0.434 / Num. unique obs: 5012 / % possible all: 99.1

-
Processing

Software
NameVersionClassification
XDSdata reduction
XSCALEdata scaling
REFMAC5.8.0049refinement
Coot0.8.2model building
RefinementResolution: 2.19→45.2 Å / Cor.coef. Fo:Fc: 0.945 / Cor.coef. Fo:Fc free: 0.925 / SU B: 7.105 / SU ML: 0.179 / Cross valid method: THROUGHOUT / ESU R: 0.283 / ESU R Free: 0.233 / Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS
RfactorNum. reflection% reflectionSelection details
Rfree0.27646 1437 7.8 %RANDOM
Rwork0.22334 ---
obs0.22743 16947 99.15 %-
Solvent computationIon probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å
Displacement parametersBiso mean: 52.878 Å2
Baniso -1Baniso -2Baniso -3
1-0.15 Å20.08 Å2-0 Å2
2--0.15 Å2-0 Å2
3----0.5 Å2
Refinement stepCycle: LAST / Resolution: 2.19→45.2 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms2319 0 30 73 2422
Refine LS restraints
Refine-IDTypeDev idealDev ideal targetNumber
X-RAY DIFFRACTIONr_bond_refined_d0.0090.0192348
X-RAY DIFFRACTIONr_bond_other_d0.0010.022241
X-RAY DIFFRACTIONr_angle_refined_deg1.3181.973188
X-RAY DIFFRACTIONr_angle_other_deg2.54435109
X-RAY DIFFRACTIONr_dihedral_angle_1_deg5.285284
X-RAY DIFFRACTIONr_dihedral_angle_2_deg34.02322.913103
X-RAY DIFFRACTIONr_dihedral_angle_3_deg12.51715372
X-RAY DIFFRACTIONr_dihedral_angle_4_deg11.0341517
X-RAY DIFFRACTIONr_chiral_restr0.0760.2343
X-RAY DIFFRACTIONr_gen_planes_refined0.0050.0212641
X-RAY DIFFRACTIONr_gen_planes_other0.0040.02573
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_it8.2826.7031148
X-RAY DIFFRACTIONr_mcbond_other8.2716.7021147
X-RAY DIFFRACTIONr_mcangle_it10.44311.2831428
X-RAY DIFFRACTIONr_mcangle_other10.44211.2851429
X-RAY DIFFRACTIONr_scbond_it9.5837.5031198
X-RAY DIFFRACTIONr_scbond_other9.5797.5061199
X-RAY DIFFRACTIONr_scangle_it
X-RAY DIFFRACTIONr_scangle_other12.42212.2681760
X-RAY DIFFRACTIONr_long_range_B_refined14.18929.9662631
X-RAY DIFFRACTIONr_long_range_B_other14.22129.9752613
X-RAY DIFFRACTIONr_rigid_bond_restr
X-RAY DIFFRACTIONr_sphericity_free
X-RAY DIFFRACTIONr_sphericity_bonded
LS refinement shellResolution: 2.19→2.247 Å / Total num. of bins used: 20
RfactorNum. reflection% reflection
Rfree0.351 102 -
Rwork0.314 1205 -
obs--97.39 %

+
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