[English] 日本語
Yorodumi
- PDB-8c7w: Crystal structure of the ACVR1 (ALK2) kinase in complex with the ... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 8c7w
TitleCrystal structure of the ACVR1 (ALK2) kinase in complex with the compound M4K2304
ComponentsActivin receptor type I
KeywordsSIGNALING PROTEIN / BMP signalling Kinase Inhibitor
Function / homology
Function and homology information


endocardial cushion cell fate commitment / mitral valve morphogenesis / BMP receptor complex / cardiac muscle cell fate commitment / BMP receptor activity / atrial septum primum morphogenesis / endocardial cushion fusion / positive regulation of cardiac epithelial to mesenchymal transition / acute inflammatory response / positive regulation of determination of dorsal identity ...endocardial cushion cell fate commitment / mitral valve morphogenesis / BMP receptor complex / cardiac muscle cell fate commitment / BMP receptor activity / atrial septum primum morphogenesis / endocardial cushion fusion / positive regulation of cardiac epithelial to mesenchymal transition / acute inflammatory response / positive regulation of determination of dorsal identity / transforming growth factor beta receptor activity, type I / smooth muscle cell differentiation / activin receptor complex / activin receptor activity, type I / endocardial cushion formation / pharyngeal system development / transmembrane receptor protein serine/threonine kinase activity / receptor protein serine/threonine kinase / activin binding / cellular response to BMP stimulus / activin receptor signaling pathway / negative regulation of activin receptor signaling pathway / embryonic heart tube morphogenesis / gastrulation with mouth forming second / dorsal/ventral pattern formation / transforming growth factor beta binding / determination of left/right symmetry / atrioventricular valve morphogenesis / neural crest cell migration / branching involved in blood vessel morphogenesis / ventricular septum morphogenesis / negative regulation of G1/S transition of mitotic cell cycle / SMAD binding / germ cell development / peptide hormone binding / positive regulation of intracellular signal transduction / mesoderm formation / positive regulation of SMAD protein signal transduction / regulation of ossification / positive regulation of bone mineralization / positive regulation of osteoblast differentiation / negative regulation of signal transduction / BMP signaling pathway / transforming growth factor beta receptor signaling pathway / protein tyrosine kinase binding / negative regulation of extrinsic apoptotic signaling pathway / cellular response to growth factor stimulus / apical part of cell / osteoblast differentiation / heart development / in utero embryonic development / cell differentiation / protein kinase activity / positive regulation of cell migration / cadherin binding / protein serine/threonine kinase activity / positive regulation of DNA-templated transcription / protein homodimerization activity / positive regulation of transcription by RNA polymerase II / ATP binding / metal ion binding / plasma membrane
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
Chem-U0C / Activin receptor type-1
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.26 Å
AuthorsCros, J. / Williams, E.P. / Sweeney, M.N. / Smil, D. / Gonzalez-Alvarez, H. / Al-awar, R. / Bullock, A.N.
Funding support Switzerland, 1items
OrganizationGrant numberCountry
Innovative Medicines Initiative Switzerland
CitationJournal: J.Med.Chem. / Year: 2024
Title: Discovery of Conformationally Constrained ALK2 Inhibitors.
Authors: Gonzalez-Alvarez, H. / Ensan, D. / Xin, T. / Wong, J.F. / Zepeda-Velazquez, C.A. / Cros, J. / Sweeney, M.N. / Hoffer, L. / Kiyota, T. / Wilson, B.J. / Aman, A. / Roberts, O. / Isaac, M.B. / ...Authors: Gonzalez-Alvarez, H. / Ensan, D. / Xin, T. / Wong, J.F. / Zepeda-Velazquez, C.A. / Cros, J. / Sweeney, M.N. / Hoffer, L. / Kiyota, T. / Wilson, B.J. / Aman, A. / Roberts, O. / Isaac, M.B. / Bullock, A.N. / Smil, D. / Al-Awar, R.
History
DepositionJan 17, 2023Deposition site: PDBE / Processing site: PDBE
Revision 1.0Feb 8, 2023Provider: repository / Type: Initial release
Revision 1.1Feb 7, 2024Group: Data collection / Category: chem_comp_atom / chem_comp_bond
Revision 1.2Aug 14, 2024Group: Database references / Category: citation / citation_author
Item: _citation.country / _citation.journal_abbrev ..._citation.country / _citation.journal_abbrev / _citation.journal_id_ASTM / _citation.journal_id_CSD / _citation.journal_id_ISSN / _citation.journal_volume / _citation.page_first / _citation.page_last / _citation.pdbx_database_id_DOI / _citation.pdbx_database_id_PubMed / _citation.title / _citation.year

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Activin receptor type I
hetero molecules


Theoretical massNumber of molelcules
Total (without water)35,91913
Polymers34,5381
Non-polymers1,38112
Water3,207178
1


  • Idetical with deposited unit
  • defined by author
  • Evidence: gel filtration, Runs as a monomer in gel filtration
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area1740 Å2
ΔGint-64 kcal/mol
Surface area14170 Å2
Unit cell
Length a, b, c (Å)66.054, 66.054, 145.926
Angle α, β, γ (deg.)90.000, 90.000, 120.000
Int Tables number154
Space group name H-MP3221
Space group name HallP322"
Symmetry operation#1: x,y,z
#2: -y,x-y,z+2/3
#3: -x+y,-x,z+1/3
#4: x-y,-y,-z+1/3
#5: -x,-x+y,-z+2/3
#6: y,x,-z

-
Components

#1: Protein Activin receptor type I


Mass: 34537.633 Da / Num. of mol.: 1 / Mutation: Q207D
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: ACVR1 / Plasmid: pFB-LIC-Bse / Cell line (production host): Sf9 / Production host: Spodoptera frugiperda (fall armyworm)
References: UniProt: Q04771, receptor protein serine/threonine kinase
#2: Chemical ChemComp-U0C / 6-methyl-9-piperazin-1-yl-4-(3,4,5-trimethoxyphenyl)-5,7-dihydropyrido[4,3-d][2]benzazepine


Mass: 460.568 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C27H32N4O3 / Feature type: SUBJECT OF INVESTIGATION
#3: Chemical
ChemComp-SO4 / SULFATE ION


Mass: 96.063 Da / Num. of mol.: 7 / Source method: obtained synthetically / Formula: SO4
#4: Chemical
ChemComp-EDO / 1,2-ETHANEDIOL / ETHYLENE GLYCOL


Mass: 62.068 Da / Num. of mol.: 4 / Source method: obtained synthetically / Formula: C2H6O2
#5: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 178 / Source method: isolated from a natural source / Formula: H2O
Has ligand of interestY

-
Experimental details

-
Experiment

ExperimentMethod: X-RAY DIFFRACTION / Number of used crystals: 1

-
Sample preparation

CrystalDensity Matthews: 2.66 Å3/Da / Density % sol: 53.86 %
Crystal growTemperature: 277 K / Method: vapor diffusion, sitting drop / pH: 8.5
Details: 1.6M ammonium sulfate, 0.1M tris pH 8.5, 4% glycerol

-
Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: Diamond / Beamline: I03 / Wavelength: 0.976254 Å
DetectorType: DECTRIS EIGER2 XE 16M / Detector: PIXEL / Date: Sep 17, 2022
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.976254 Å / Relative weight: 1
ReflectionResolution: 2.26→57.2 Å / Num. obs: 17992 / % possible obs: 100 % / Redundancy: 20.03 % / Biso Wilson estimate: 33.11 Å2 / CC1/2: 0.9883 / Rmerge(I) obs: 0.4368 / Net I/σ(I): 3.6
Reflection shellResolution: 2.26→2.3 Å / Redundancy: 20.62 % / Rmerge(I) obs: 2.1056 / Mean I/σ(I) obs: 0.54 / Num. unique obs: 874 / CC1/2: 0.8165 / % possible all: 98.76

-
Processing

Software
NameVersionClassification
PHENIX1.20.1_4487refinement
xia2data reduction
DIALSdata scaling
PHASER1.20.1_4487phasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 3MTF

3mtf


Resolution: 2.26→57.2 Å / SU ML: 0.3373 / Cross valid method: FREE R-VALUE / σ(F): 1.34 / Phase error: 25.7702
Stereochemistry target values: GeoStd + Monomer Library + CDL v1.2
RfactorNum. reflection% reflection
Rfree0.2392 871 4.86 %
Rwork0.207 17047 -
obs0.2086 17918 99.75 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.1 Å / Solvent model: FLAT BULK SOLVENT MODEL
Displacement parametersBiso mean: 32.59 Å2
Refinement stepCycle: LAST / Resolution: 2.26→57.2 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms2330 0 85 178 2593
Refine LS restraints
Refine-IDTypeDev idealNumber
X-RAY DIFFRACTIONf_bond_d0.00222481
X-RAY DIFFRACTIONf_angle_d0.56683377
X-RAY DIFFRACTIONf_chiral_restr0.0401374
X-RAY DIFFRACTIONf_plane_restr0.0035418
X-RAY DIFFRACTIONf_dihedral_angle_d15.4662346
LS refinement shell
Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkRefine-ID% reflection obs (%)
2.26-2.40.30991480.29962761X-RAY DIFFRACTION99.39
2.4-2.590.34961400.27162797X-RAY DIFFRACTION99.76
2.59-2.850.29721380.25482801X-RAY DIFFRACTION99.59
2.85-3.260.27241380.20922828X-RAY DIFFRACTION99.9
3.26-4.10.20891620.17982856X-RAY DIFFRACTION100
4.11-57.20.18331450.17083004X-RAY DIFFRACTION99.94

+
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