[English] 日本語
Yorodumi
- PDB-6eix: Crystal structure of the kinase domain of the Q207E mutant of ACV... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 6eix
TitleCrystal structure of the kinase domain of the Q207E mutant of ACVR1 (ALK2) in complex with a 2-aminopyridine inhibitor K02288
ComponentsActivin receptor type-1
KeywordsSIGNALING PROTEIN / Kinase / ALK2 / Receptor / BMP / Structural Genomics / Structural Genomics Consortium / SGC
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 / BMP signaling pathway / negative regulation of signal transduction / 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 / Protein tyrosine and serine/threonine kinase / 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 / Protein tyrosine and serine/threonine kinase / 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-A3F / Activin receptor type-1
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.3 Å
AuthorsWilliams, E.P. / Canning, P. / Sanvitale, C.E. / Krojer, T. / Allerston, C.K. / von Delft, F. / Arrowsmith, C.H. / Edwards, A.M. / Bountra, C. / Bullock, A.N.
CitationJournal: To be published
Title: Crystal structure of the kinase domain of the Q207E mutant of ACVR1 (ALK2) in complex with K02288
Authors: Williams, E.P. / Canning, P. / Sanvitale, C.E. / Bullock, A.N.
History
DepositionSep 19, 2017Deposition site: PDBE / Processing site: PDBE
Revision 1.0Sep 27, 2017Provider: repository / Type: Initial release
Revision 1.1Dec 13, 2017Group: Structure summary / Category: audit_author / Item: _audit_author.name
Revision 1.2Feb 28, 2018Group: Source and taxonomy / Category: entity_src_gen
Item: _entity_src_gen.pdbx_host_org_cell_line / _entity_src_gen.pdbx_host_org_strain
Revision 1.3Jan 17, 2024Group: Data collection / Database references / Refinement description
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / database_2 / pdbx_initial_refinement_model
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Activin receptor type-1
hetero molecules


Theoretical massNumber of molelcules
Total (without water)39,43111
Polymers38,5201
Non-polymers91110
Water1,15364
1


  • Idetical with deposited unit
  • defined by software
  • Evidence: gel filtration, mass spectrometry
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area1790 Å2
ΔGint29 kcal/mol
Surface area14280 Å2
MethodPISA
Unit cell
Length a, b, c (Å)81.560, 66.990, 62.220
Angle α, β, γ (deg.)90.00, 91.04, 90.00
Int Tables number5
Space group name H-MC121

-
Components

#1: Protein Activin receptor type-1 / Activin receptor type I / ACTR-I / Activin receptor-like kinase 2 / ALK-2 / Serine/threonine- ...Activin receptor type I / ACTR-I / Activin receptor-like kinase 2 / ALK-2 / Serine/threonine-protein kinase receptor R1 / SKR1 / TGF-B superfamily receptor type I / TSR-I


Mass: 38520.000 Da / Num. of mol.: 1 / Mutation: Q207E
Source method: isolated from a genetically manipulated source
Details: Missing residues at N and C terminus due to insufficient density to model them.
Source: (gene. exp.) Homo sapiens (human) / Gene: ACVR1, ACVRLK2 / 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-A3F / 3-[6-amino-5-(3,4,5-trimethoxyphenyl)pyridin-3-yl]phenol


Mass: 352.384 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C20H20N2O4 / Feature type: SUBJECT OF INVESTIGATION
#3: Chemical
ChemComp-EDO / 1,2-ETHANEDIOL / ETHYLENE GLYCOL


Mass: 62.068 Da / Num. of mol.: 9 / Source method: obtained synthetically / Formula: C2H6O2
#4: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 64 / 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: 2.21 Å3/Da / Density % sol: 44.35 %
Crystal growTemperature: 293 K / Method: vapor diffusion, sitting drop / pH: 6.5 / Details: 0.1M MES pH 6.5 -- 12%(w/v) PEG 20000

-
Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: SYNCHROTRON / Site: Diamond / Beamline: I03 / Wavelength: 0.9778 Å
DetectorType: DECTRIS PILATUS 6M / Detector: PIXEL / Date: Apr 21, 2012
Details: Kirkpatrick Baez bimorph mirror pair for horizontal and vertical focussing
RadiationMonochromator: Double Crystal / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.9778 Å / Relative weight: 1
ReflectionResolution: 2.3→19.78 Å / Num. obs: 14813 / % possible obs: 98.9 % / Observed criterion σ(I): 2 / Redundancy: 3 % / CC1/2: 0.984 / Rmerge(I) obs: 0.122 / Rpim(I) all: 0.082 / Rrim(I) all: 0.148 / Net I/σ(I): 5.4
Reflection shellResolution: 2.3→2.38 Å / Redundancy: 3.1 % / Rmerge(I) obs: 0.511 / Mean I/σ(I) obs: 2.2 / Num. unique obs: 1444 / CC1/2: 0.749 / Rpim(I) all: 0.344 / Rrim(I) all: 0.619 / % possible all: 99.1

-
Processing

Software
NameVersionClassification
REFMAC5.7.0032refinement
iMOSFLM7.2.1data reduction
Aimless7.0.044data scaling
PHASER7.0.044phasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 1IAS

1ias


Resolution: 2.3→19.78 Å / Cor.coef. Fo:Fc: 0.946 / Cor.coef. Fo:Fc free: 0.892 / SU B: 13.579 / SU ML: 0.17 / SU R Cruickshank DPI: 0.3761 / Cross valid method: THROUGHOUT / ESU R: 0.376 / ESU R Free: 0.253 / SU Rfree Cruickshank DPI: 0.2529 / Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS
RfactorNum. reflection% reflectionSelection details
Rfree0.24944 749 5.1 %RANDOM
Rwork0.18825 ---
obs0.19135 14001 98.39 %-
Solvent computationIon probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å
Displacement parametersBiso mean: 33.214 Å2
Baniso -1Baniso -2Baniso -3
1--0.83 Å20 Å20.08 Å2
2---3.68 Å20 Å2
3---4.51 Å2
Refinement stepCycle: 1 / Resolution: 2.3→19.78 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms2464 0 62 64 2590
Refine LS restraints
Refine-IDTypeDev idealDev ideal targetNumber
X-RAY DIFFRACTIONr_bond_refined_d0.0070.0192583
X-RAY DIFFRACTIONr_bond_other_d0.0010.022459
X-RAY DIFFRACTIONr_angle_refined_deg1.1291.9673491
X-RAY DIFFRACTIONr_angle_other_deg0.72235638
X-RAY DIFFRACTIONr_dihedral_angle_1_deg6.0845313
X-RAY DIFFRACTIONr_dihedral_angle_2_deg31.66124.018112
X-RAY DIFFRACTIONr_dihedral_angle_3_deg13.45715437
X-RAY DIFFRACTIONr_dihedral_angle_4_deg21.951516
X-RAY DIFFRACTIONr_chiral_restr0.0630.2388
X-RAY DIFFRACTIONr_gen_planes_refined0.0040.0212878
X-RAY DIFFRACTIONr_gen_planes_other0.0010.02591
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_it4.1318.521252
X-RAY DIFFRACTIONr_mcbond_other4.1288.5111251
X-RAY DIFFRACTIONr_mcangle_it5.34612.4321565
X-RAY DIFFRACTIONr_mcangle_other5.34612.4411566
X-RAY DIFFRACTIONr_scbond_it4.7089.2571331
X-RAY DIFFRACTIONr_scbond_other4.699.2581331
X-RAY DIFFRACTIONr_scangle_it
X-RAY DIFFRACTIONr_scangle_other6.25813.1021927
X-RAY DIFFRACTIONr_long_range_B_refined7.59129.1682950
X-RAY DIFFRACTIONr_long_range_B_other7.5929.1812951
X-RAY DIFFRACTIONr_rigid_bond_restr
X-RAY DIFFRACTIONr_sphericity_free
X-RAY DIFFRACTIONr_sphericity_bonded
LS refinement shellResolution: 2.3→2.36 Å
RfactorNum. reflection% reflection
Rfree0.277 47 5 %
Rwork0.218 994 -
obs--97.56 %
Refinement TLS params.Method: refined / Origin x: 19.4143 Å / Origin y: 19.0257 Å / Origin z: -18.2558 Å
111213212223313233
T0.0456 Å2-0.0136 Å2-0.0042 Å2-0.0619 Å2-0.0224 Å2--0.0907 Å2
L0.5775 °20.2082 °2-0.2425 °2-0.4149 °2-0.004 °2--0.1575 °2
S0.0635 Å °-0.1033 Å °0.0422 Å °-0.0283 Å °-0.071 Å °0.0514 Å °-0.0079 Å °0.0349 Å °0.0075 Å °
Refinement TLS group
IDRefine-IDRefine TLS-IDAuth asym-IDAuth seq-ID
1X-RAY DIFFRACTION1A172 - 196
2X-RAY DIFFRACTION1A197 - 258
3X-RAY DIFFRACTION1A259 - 297
4X-RAY DIFFRACTION1A298 - 359
5X-RAY DIFFRACTION1A360 - 377
6X-RAY DIFFRACTION1A378 - 499

+
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