[English] 日本語
Yorodumi
- PDB-5usq: ALK-5 kinase inhibitor complex -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 5usq
TitleALK-5 kinase inhibitor complex
ComponentsTGF-beta receptor type-1
KeywordsTransferase/Transferase Inhibitor / TGF-beta receptor type I / Serine/threonine-protein kinase receptor R4 / Activin receptor-like kinase 5 / Transferase-Transferase Inhibitor complex
Function / homology
Function and homology information


extracellular structure organization / epicardium morphogenesis / parathyroid gland development / transforming growth factor beta ligand-receptor complex / regulation of cardiac muscle cell proliferation / myofibroblast differentiation / positive regulation of tight junction disassembly / 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 / parathyroid gland development / transforming growth factor beta ligand-receptor complex / regulation of cardiac muscle cell proliferation / myofibroblast differentiation / positive regulation of tight junction disassembly / positive regulation of epithelial to mesenchymal transition involved in endocardial cushion formation / TGFBR2 Kinase Domain Mutants in Cancer / transforming growth factor beta receptor activity / positive regulation of mesenchymal stem cell proliferation / ventricular compact myocardium morphogenesis / SMAD2/3 Phosphorylation Motif Mutants in Cancer / TGFBR1 KD Mutants in Cancer / positive regulation of vasculature development / regulation of epithelial to mesenchymal transition / activin receptor activity, type I / cardiac epithelial to mesenchymal transition / transforming growth factor beta receptor activity, type I / activin receptor complex / mesenchymal cell differentiation / neuron fate commitment / germ cell migration / positive regulation of extracellular matrix assembly / type II transforming growth factor beta receptor binding / TGFBR1 LBD Mutants in Cancer / angiogenesis involved in coronary vascular morphogenesis / receptor protein serine/threonine kinase / transmembrane receptor protein serine/threonine kinase activity / pharyngeal system development / activin binding / coronary artery morphogenesis / activin receptor signaling pathway / filopodium assembly / ventricular trabecula myocardium morphogenesis / transforming growth factor beta binding / embryonic cranial skeleton morphogenesis / response to cholesterol / I-SMAD binding / negative regulation of chondrocyte differentiation / collagen fibril organization / endothelial cell proliferation / endothelial cell activation / skeletal system morphogenesis / lens development in camera-type eye / positive regulation of filopodium assembly / anterior/posterior pattern specification / artery morphogenesis / ventricular septum morphogenesis / roof of mouth development / TGF-beta receptor signaling activates SMADs / SMAD binding / negative regulation of endothelial cell proliferation / positive regulation of SMAD protein signal transduction / blastocyst development / regulation of protein ubiquitination / endothelial cell migration / bicellular tight junction / epithelial to mesenchymal transition / positive regulation of epithelial to mesenchymal transition / positive regulation of apoptotic signaling pathway / positive regulation of stress fiber assembly / cellular response to transforming growth factor beta stimulus / positive regulation of endothelial cell proliferation / Downregulation of TGF-beta receptor signaling / post-embryonic development / transforming growth factor beta receptor signaling pathway / negative regulation of cell migration / thymus development / TGF-beta receptor signaling in EMT (epithelial to mesenchymal transition) / kidney development / skeletal system development / cell motility / negative regulation of extrinsic apoptotic signaling pathway / wound healing / cellular response to growth factor stimulus / male gonad development / UCH proteinases / nervous system development / heart development / positive regulation of cell growth / regulation of gene expression / peptidyl-serine phosphorylation / in utero embryonic development / positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction / receptor complex / regulation of cell cycle / Ub-specific processing proteases / endosome / protein kinase activity / intracellular signal transduction / positive regulation of cell migration / membrane raft / protein serine/threonine kinase activity / apoptotic process / ubiquitin protein ligase binding / positive regulation of cell population proliferation / positive regulation of gene expression / regulation of DNA-templated transcription / positive regulation of DNA-templated transcription
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 / Transferase(Phosphotransferase) domain 1 / Transferase(Phosphotransferase); 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 / Transferase(Phosphotransferase) domain 1 / Transferase(Phosphotransferase); domain 1 / Phosphorylase Kinase; domain 1 / Phosphorylase Kinase; 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
Chem-8LY / TGF-beta receptor type-1
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / Resolution: 2.55 Å
AuthorsDougan, D.R. / Lawson, J.D.
CitationJournal: Bioorg. Med. Chem. Lett. / Year: 2017
Title: Design, synthesis and optimization of 7-substituted-pyrazolo[4,3-b]pyridine ALK5 (activin receptor-like kinase 5) inhibitors.
Authors: Sabat, M. / Wang, H. / Scorah, N. / Lawson, J.D. / Atienza, J. / Kamran, R. / Hixon, M.S. / Dougan, D.R.
History
DepositionFeb 13, 2017Deposition site: RCSB / Processing site: RCSB
Revision 1.0Apr 12, 2017Provider: repository / Type: Initial release
Revision 1.1Apr 26, 2017Group: Database references
Revision 1.2Nov 22, 2017Group: Refinement description / Category: software / Item: _software.name
Revision 1.3Mar 6, 2024Group: Data collection / Database references / Refinement description
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / database_2 / refine_hist
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession / _refine_hist.d_res_low

-
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)34,7022
Polymers34,2651
Non-polymers4371
Water1,874104
1


  • Idetical with deposited unit
  • defined by author&software
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
Unit cell
Length a, b, c (Å)41.589, 78.330, 90.712
Angle α, β, γ (deg.)90.000, 90.000, 90.000
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: 34265.398 Da / Num. of mol.: 1 / Fragment: UNP residues 123-421
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: TGFBR1, ALK5, SKR4 / Production host: unidentified baculovirus
References: UniProt: P36897, receptor protein serine/threonine kinase
#2: Chemical ChemComp-8LY / N-[2-(5-chloro-2-fluorophenyl)pyridin-4-yl]-2-[(piperidin-4-yl)methyl]-2H-pyrazolo[4,3-b]pyridin-7-amine


Mass: 436.912 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C23H22ClFN6
#3: Water ChemComp-HOH / water / Water


Mass: 18.015 Da / Num. of mol.: 104 / 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: 2.16 Å3/Da / Density % sol: 42.95 %
Crystal growTemperature: 293 K / Method: vapor diffusion, sitting drop / pH: 9.2 / Details: 16 % PEG 8000 100mM CHES pH 9.2 / PH range: 9.0 -9.4

-
Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: SYNCHROTRON / Site: ALS / Beamline: 5.0.3 / Wavelength: 0.9765 Å
DetectorType: ADSC QUANTUM 315r / Detector: CCD / Date: Nov 5, 2009
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.9765 Å / Relative weight: 1
ReflectionResolution: 2.55→50 Å / Num. obs: 10064 / % possible obs: 98.8 % / Redundancy: 4.9 % / Rmerge(I) obs: 0.137 / Χ2: 1.021 / Net I/σ(I): 6.9 / Num. measured all: 49464
Reflection shell
Resolution (Å)Redundancy (%)Rmerge(I) obsΧ2Diffraction-ID% possible all
2.55-2.592.90.4130.95187.6
2.59-2.643.40.4280.948193.5
2.64-2.693.90.4010.95197.2
2.69-2.754.40.4181.039198.2
2.75-2.814.70.3791.058199.2
2.81-2.875.10.3621.037199.8
2.87-2.945.20.321.048199.8
2.94-3.025.40.2780.991100
3.02-3.115.50.271.11100
3.11-3.215.40.2091.051199.8
3.21-3.335.40.181.0421100
3.33-3.465.30.1451.0251100
3.46-3.625.40.1181.021199.8
3.62-3.815.30.1021.002199.8
3.81-4.055.40.0931.0121100
4.05-4.365.20.0831.0211100
4.36-4.85.20.0820.9951100
4.8-5.495.20.0891.0121100
5.49-6.924.90.11.0421100
6.92-504.70.0520.979199.7

-
Processing

Software
NameVersionClassification
HKL-2000data collection
HKL-2000data scaling
REFMAC5.8.0135refinement
PDB_EXTRACT3.22data extraction
HKL-2000data reduction
DENZOdata reduction
SCALEPACKdata scaling
RefinementResolution: 2.55→45.35 Å / Cor.coef. Fo:Fc: 0.943 / Cor.coef. Fo:Fc free: 0.904 / WRfactor Rfree: 0.2162 / WRfactor Rwork: 0.1675 / FOM work R set: 0.83 / SU B: 21.203 / SU ML: 0.229 / SU R Cruickshank DPI: 0.242 / SU Rfree: 0.3099 / Cross valid method: THROUGHOUT / σ(F): 0 / ESU R Free: 0.31 / Stereochemistry target values: MAXIMUM LIKELIHOOD
Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS U VALUES : WITH TLS ADDED
RfactorNum. reflection% reflectionSelection details
Rfree0.2305 482 4.8 %RANDOM
Rwork0.1792 ---
obs0.1817 9545 98.77 %-
Solvent computationIon probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å / Solvent model: MASK
Displacement parametersBiso max: 86.7 Å2 / Biso mean: 28.686 Å2 / Biso min: 9.83 Å2
Baniso -1Baniso -2Baniso -3
1--1.47 Å20 Å2-0 Å2
2--0.32 Å20 Å2
3---1.15 Å2
Refinement stepCycle: final / Resolution: 2.55→45.35 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms2404 0 31 104 2539
Biso mean--24.73 26.35 -
Num. residues----299
Refine LS restraints
Refine-IDTypeDev idealDev ideal targetNumber
X-RAY DIFFRACTIONr_bond_refined_d0.0070.0192496
X-RAY DIFFRACTIONr_bond_other_d0.0020.022379
X-RAY DIFFRACTIONr_angle_refined_deg1.1941.9553373
X-RAY DIFFRACTIONr_angle_other_deg0.89235455
X-RAY DIFFRACTIONr_dihedral_angle_1_deg5.9155298
X-RAY DIFFRACTIONr_dihedral_angle_2_deg33.04822.931116
X-RAY DIFFRACTIONr_dihedral_angle_3_deg13.36815447
X-RAY DIFFRACTIONr_dihedral_angle_4_deg13.8881523
X-RAY DIFFRACTIONr_chiral_restr0.0650.2365
X-RAY DIFFRACTIONr_gen_planes_refined0.0040.022789
X-RAY DIFFRACTIONr_gen_planes_other0.0010.02592
LS refinement shellResolution: 2.551→2.617 Å / Rfactor Rfree error: 0 / Total num. of bins used: 20
RfactorNum. reflection% reflection
Rfree0.299 36 -
Rwork0.24 628 -
all-664 -
obs--89.25 %
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)
10.03130.1385-0.06061.036-0.13640.39130.0062-0.012-0.0178-0.0306-0.0221-0.01330.01910.06020.01590.0168-0.0053-0.01320.0323-0.01640.050912.432861.7153.3628
20.48270.16010.24140.49260.3320.50020.0181-0.02970.0955-0.0082-0.03280.0447-0.0052-0.02380.01470.01290.0089-0.01230.0108-0.02080.049911.326783.388516.1773
Refinement TLS group
IDRefine-IDRefine TLS-IDAuth asym-IDAuth seq-ID
1X-RAY DIFFRACTION1A200 - 279
2X-RAY DIFFRACTION2A280 - 498

+
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