[English] 日本語
Yorodumi
- PDB-4x2n: Selection of fragments for kinase inhibitor design: decoration is key -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 4x2n
TitleSelection of fragments for kinase inhibitor design: decoration is key
ComponentsTGF-beta receptor type-1
KeywordsTRANSFERASE / PROTEIN KINASE / INHIBITOR COMPLEX
Function / homology
Function and homology information


extracellular structure organization / epicardium morphogenesis / vascular endothelial cell proliferation / parathyroid gland development / transforming growth factor beta ligand-receptor complex / regulation of cardiac muscle cell proliferation / myofibroblast differentiation / positive regulation of epithelial to mesenchymal transition involved in endocardial cushion formation / TGFBR2 Kinase Domain Mutants in Cancer / transforming growth factor beta receptor activity ...extracellular structure organization / epicardium morphogenesis / vascular endothelial cell proliferation / parathyroid gland development / transforming growth factor beta ligand-receptor complex / regulation of cardiac muscle cell proliferation / myofibroblast differentiation / positive regulation of epithelial to mesenchymal transition involved in endocardial cushion formation / TGFBR2 Kinase Domain Mutants in Cancer / transforming growth factor beta receptor activity / trophoblast cell migration / angiogenesis involved in coronary vascular morphogenesis / SMAD2/3 Phosphorylation Motif Mutants in Cancer / TGFBR1 KD Mutants in Cancer / positive regulation of mesenchymal stem cell proliferation / ventricular compact myocardium morphogenesis / positive regulation of extracellular matrix assembly / positive regulation of tight junction disassembly / TGFBR3 regulates TGF-beta signaling / cardiac epithelial to mesenchymal transition / mesenchymal cell differentiation / transforming growth factor beta receptor activity, type I / positive regulation of vasculature development / neuron fate commitment / activin receptor complex / activin receptor activity, type I / regulation of epithelial to mesenchymal transition / type II transforming growth factor beta receptor binding / pharyngeal system development / transmembrane receptor protein serine/threonine kinase activity / receptor protein serine/threonine kinase / activin binding / TGFBR1 LBD Mutants in Cancer / germ cell migration / filopodium assembly / coronary artery morphogenesis / embryonic cranial skeleton morphogenesis / activin receptor signaling pathway / ventricular trabecula myocardium morphogenesis / response to cholesterol / I-SMAD binding / transforming growth factor beta binding / collagen fibril organization / negative regulation of chondrocyte differentiation / lens development in camera-type eye / endothelial cell activation / anterior/posterior pattern specification / positive regulation of filopodium assembly / artery morphogenesis / skeletal system morphogenesis / ventricular septum morphogenesis / SMAD binding / negative regulation of endothelial cell proliferation / TGF-beta receptor signaling activates SMADs / roof of mouth development / positive regulation of SMAD protein signal transduction / blastocyst development / epithelial to mesenchymal transition / regulation of protein ubiquitination / bicellular tight junction / endothelial cell migration / cellular response to transforming growth factor beta stimulus / positive regulation of epithelial to mesenchymal transition / positive regulation of stress fiber assembly / positive regulation of endothelial cell proliferation / transforming growth factor beta receptor signaling pathway / negative regulation of cell migration / thymus development / Downregulation of TGF-beta receptor signaling / positive regulation of apoptotic signaling pathway / TGF-beta receptor signaling in EMT (epithelial to mesenchymal transition) / post-embryonic development / skeletal system development / negative regulation of extrinsic apoptotic signaling pathway / kidney development / cell motility / wound healing / peptidyl-serine phosphorylation / cellular response to growth factor stimulus / male gonad development / UCH proteinases / nervous system development / heart development / regulation of gene expression / positive regulation of cell growth / in utero embryonic development / positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction / receptor complex / protein kinase activity / regulation of cell cycle / endosome / Ub-specific processing proteases / intracellular signal transduction / cilium / positive regulation of cell migration / membrane raft / protein serine/threonine kinase activity / positive regulation of cell population proliferation / apoptotic process / ubiquitin protein ligase binding
Similarity search - Function
GS domain / Transforming growth factor beta type I GS-motif / GS domain profile. / GS motif / Activin types I and II receptor domain / Activin types I and II receptor domain / Ser/Thr protein kinase, TGFB receptor / Snake toxin-like superfamily / Phosphorylase Kinase; domain 1 / Phosphorylase Kinase; domain 1 ...GS domain / Transforming growth factor beta type I GS-motif / GS domain profile. / GS motif / Activin types I and II receptor domain / Activin types I and II receptor domain / Ser/Thr protein kinase, TGFB receptor / Snake toxin-like superfamily / Phosphorylase Kinase; domain 1 / Phosphorylase Kinase; domain 1 / Transferase(Phosphotransferase) domain 1 / Transferase(Phosphotransferase); domain 1 / Serine/threonine-protein kinase, active site / Serine/Threonine protein kinases active-site signature. / Protein kinase domain / Serine/Threonine protein kinases, catalytic domain / Protein kinase, ATP binding site / Protein kinases ATP-binding region signature. / 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
TGF-beta receptor type-1
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / Resolution: 1.8 Å
AuthorsCzodrowski, P. / Hoelzemann, G. / Barnickel, G. / Greiner, H. / Musil, D.
CitationJournal: J.Med.Chem. / Year: 2015
Title: Selection of fragments for kinase inhibitor design: decoration is key.
Authors: Czodrowski, P. / Holzemann, G. / Barnickel, G. / Greiner, H. / Musil, D.
History
DepositionNov 26, 2014Deposition site: RCSB / Processing site: PDBE
Revision 1.0Dec 24, 2014Provider: repository / Type: Initial release
Revision 1.1Jan 21, 2015Group: Database references
Revision 1.2May 8, 2024Group: Data collection / Database references / Category: chem_comp_atom / chem_comp_bond / database_2
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: TGF-beta receptor type-1
hetero molecules


Theoretical massNumber of molelcules
Total (without water)34,9782
Polymers34,8821
Non-polymers961
Water5,765320
1


  • Idetical with deposited unit
  • defined by author&software
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area220 Å2
ΔGint-17 kcal/mol
Surface area14490 Å2
MethodPISA
Unit cell
Length a, b, c (Å)41.810, 77.890, 90.250
Angle α, β, γ (deg.)90.00, 90.00, 90.00
Int Tables number19
Space group name H-MP212121

-
Components

#1: Protein TGF-beta receptor type-1 / TGFR-1 / Activin A receptor type II-like protein kinase of 53kD / Activin receptor-like kinase 5 / ...TGFR-1 / Activin A receptor type II-like protein kinase of 53kD / Activin receptor-like kinase 5 / ALK5 / Serine/threonine-protein kinase receptor R4 / SKR4 / TGF-beta type I receptor / Transforming growth factor-beta receptor type I / TbetaR-I


Mass: 34882.148 Da / Num. of mol.: 1 / Fragment: UNP residues 200-503
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: TGFBR1, ALK5, SKR4 / Production host: Spodoptera frugiperda (fall armyworm)
References: UniProt: P36897, receptor protein serine/threonine kinase
#2: Chemical ChemComp-SO4 / SULFATE ION


Mass: 96.063 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: SO4
#3: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 320 / Source method: isolated from a natural source / Formula: H2O

-
Experimental details

-
Experiment

ExperimentMethod: X-RAY DIFFRACTION

-
Sample preparation

CrystalDensity Matthews: 2.11 Å3/Da / Density % sol: 41.61 %
Crystal growTemperature: 293 K / Method: vapor diffusion, hanging drop / pH: 7.5
Details: 0.1 M Tris-HCl, 240 mM Li2SO4, 24% PEG 4000, pH 7.5
PH range: 7.5

-
Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: ROTATING ANODE / Type: OTHER / Wavelength: 1.5418 Å
DetectorType: RIGAKU SATURN 944+ / Detector: CCD / Date: Jun 3, 2008
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1.5418 Å / Relative weight: 1
ReflectionResolution: 1.63→37.94 Å / Num. obs: 30203 / % possible obs: 70 % / Redundancy: 2 % / Biso Wilson estimate: 15.98 Å2 / Net I/σ(I): 13.3

-
Processing

Software
NameVersionClassification
BUSTER2.11.4refinement
XDSdata reduction
XSCALEdata scaling
RefinementResolution: 1.8→21.41 Å / Cor.coef. Fo:Fc: 0.9516 / Cor.coef. Fo:Fc free: 0.9248 / SU R Cruickshank DPI: 0.126 / Cross valid method: THROUGHOUT / σ(F): 0 / SU R Blow DPI: 0.139 / SU Rfree Blow DPI: 0.125 / SU Rfree Cruickshank DPI: 0.12
RfactorNum. reflection% reflectionSelection details
Rfree0.2012 1309 4.97 %RANDOM
Rwork0.161 ---
obs0.1629 26319 93.86 %-
Displacement parametersBiso mean: 17.06 Å2
Baniso -1Baniso -2Baniso -3
1--0.7667 Å20 Å20 Å2
2---0.5696 Å20 Å2
3---1.3364 Å2
Refine analyzeLuzzati coordinate error obs: 0.182 Å
Refinement stepCycle: 1 / Resolution: 1.8→21.41 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms2444 0 5 320 2769
Refine LS restraints
Refine-IDTypeDev idealNumberRestraint functionWeight
X-RAY DIFFRACTIONt_bond_d0.012501HARMONIC2
X-RAY DIFFRACTIONt_angle_deg0.983381HARMONIC2
X-RAY DIFFRACTIONt_dihedral_angle_d897SINUSOIDAL2
X-RAY DIFFRACTIONt_incorr_chiral_ct
X-RAY DIFFRACTIONt_pseud_angle
X-RAY DIFFRACTIONt_trig_c_planes60HARMONIC2
X-RAY DIFFRACTIONt_gen_planes365HARMONIC5
X-RAY DIFFRACTIONt_it2501HARMONIC20
X-RAY DIFFRACTIONt_nbd
X-RAY DIFFRACTIONt_omega_torsion3.71
X-RAY DIFFRACTIONt_other_torsion13.9
X-RAY DIFFRACTIONt_improper_torsion
X-RAY DIFFRACTIONt_chiral_improper_torsion322SEMIHARMONIC5
X-RAY DIFFRACTIONt_sum_occupancies
X-RAY DIFFRACTIONt_utility_distance
X-RAY DIFFRACTIONt_utility_angle
X-RAY DIFFRACTIONt_utility_torsion
X-RAY DIFFRACTIONt_ideal_dist_contact3228SEMIHARMONIC4
LS refinement shellResolution: 1.8→1.87 Å / Total num. of bins used: 13
RfactorNum. reflection% reflection
Rfree0.2291 121 4.82 %
Rwork0.1689 2388 -
all0.1718 2509 -
obs--93.86 %
Refinement TLS params.Method: refined / Origin x: 11.9104 Å / Origin y: -0.8862 Å / Origin z: 12.3393 Å
111213212223313233
T-0.0391 Å2-0.0055 Å2-0.0023 Å2--0.0037 Å20.0063 Å2---0.0395 Å2
L0.3395 °20.1344 °20.1597 °2-0.3604 °20.3923 °2--0.6966 °2
S-0.0332 Å °-0.0208 Å °0.0456 Å °-0.0448 Å °-0.0069 Å °0.0258 Å °-0.0819 Å °0.0086 Å °0.0401 Å °
Refinement TLS groupSelection details: { A|* }

+
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