[English] 日本語
Yorodumi
- PDB-4dym: Crystal structure of the ACVR1 kinase domain in complex with the ... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 4dym
TitleCrystal structure of the ACVR1 kinase domain in complex with the imidazo[1,2-b]pyridazine inhibitor K00135
ComponentsActivin receptor type-1
KeywordsTRANSFERASE/TRANSFERASE INHIBITOR / Structural Genomics / Structural Genomics Consortium / SGC / Protein Kinase / TRANSFERASE-TRANSFERASE INHIBITOR complex
Function / homology
Function and homology information


endocardial cushion cell fate commitment / mitral valve morphogenesis / BMP receptor complex / atrial septum primum morphogenesis / cardiac muscle cell fate commitment / endocardial cushion fusion / positive regulation of cardiac epithelial to mesenchymal transition / activin receptor complex / acute inflammatory response / positive regulation of determination of dorsal identity ...endocardial cushion cell fate commitment / mitral valve morphogenesis / BMP receptor complex / atrial septum primum morphogenesis / cardiac muscle cell fate commitment / endocardial cushion fusion / positive regulation of cardiac epithelial to mesenchymal transition / activin receptor complex / acute inflammatory response / positive regulation of determination of dorsal identity / smooth muscle cell differentiation / endocardial cushion formation / transforming growth factor beta receptor activity, type I / activin receptor activity, type I / activin receptor activity, type II / BMP receptor activity / receptor protein serine/threonine kinase / transforming growth factor beta receptor activity, type II / transmembrane receptor protein serine/threonine kinase activity / pharyngeal system development / transforming growth factor beta receptor activity, type III / 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 / neural crest cell migration / atrioventricular valve morphogenesis / ventricular septum morphogenesis / branching involved in blood vessel morphogenesis / negative regulation of G1/S transition of mitotic cell cycle / SMAD binding / germ cell development / peptide hormone binding / mesoderm formation / positive regulation of SMAD protein signal transduction / regulation of ossification / BMP signaling pathway / positive regulation of bone mineralization / positive regulation of osteoblast differentiation / 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 / positive regulation of peptidyl-tyrosine phosphorylation / osteoblast differentiation / apical part of cell / 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 / Serine/threonine-protein kinase, active site / Serine/Threonine protein kinases active-site signature. / Phosphorylase Kinase; domain 1 / Transferase(Phosphotransferase) domain 1 / Transferase(Phosphotransferase); domain 1 / 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-IYZ / Activin receptor type-1
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.42 Å
AuthorsChaikuad, A. / Sanvitale, C. / Cooper, C. / Canning, P. / Mahajan, P. / Daga, N. / Petrie, K. / Alfano, I. / Gileadi, O. / Fedorov, O. ...Chaikuad, A. / Sanvitale, C. / Cooper, C. / Canning, P. / Mahajan, P. / Daga, N. / Petrie, K. / Alfano, I. / Gileadi, O. / Fedorov, O. / Krojer, T. / Filippakopoulos, P. / Muniz, J.R.C. / von Delft, F. / Weigelt, J. / Arrowsmith, C.H. / Edwards, A.M. / Bountra, C. / Bullock, A. / Structural Genomics Consortium (SGC)
CitationJournal: To be Published
Title: Crystal structure of the ACVR1 kinase domain in complex with the imidazo[1,2-b]pyridazine inhibitor K00135
Authors: Chaikuad, A. / Sanvitale, C. / Cooper, C. / Canning, P. / Mahajan, P. / Daga, N. / Petrie, K. / Alfano, I. / Gileadi, O. / Fedorov, O. / Krojer, T. / Filippakopoulos, P. / Muniz, J.R.C. / ...Authors: Chaikuad, A. / Sanvitale, C. / Cooper, C. / Canning, P. / Mahajan, P. / Daga, N. / Petrie, K. / Alfano, I. / Gileadi, O. / Fedorov, O. / Krojer, T. / Filippakopoulos, P. / Muniz, J.R.C. / von Delft, F. / Weigelt, J. / Arrowsmith, C.H. / Edwards, A.M. / Bountra, C. / Bullock, A. / Structural Genomics Consortium (SGC)
History
DepositionFeb 29, 2012Deposition site: RCSB / Processing site: RCSB
Revision 1.0Mar 21, 2012Provider: repository / Type: Initial release
Revision 1.1Sep 13, 2023Group: Data collection / Database references ...Data collection / Database references / Derived calculations / Refinement description
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / database_2 / pdbx_initial_refinement_model / struct_ref_seq_dif / struct_site
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession ..._database_2.pdbx_DOI / _database_2.pdbx_database_accession / _struct_ref_seq_dif.details / _struct_site.pdbx_auth_asym_id / _struct_site.pdbx_auth_comp_id / _struct_site.pdbx_auth_seq_id

-
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)35,3988
Polymers34,5321
Non-polymers8677
Water2,234124
1
A: Activin receptor type-1
hetero molecules

A: Activin receptor type-1
hetero molecules


Theoretical massNumber of molelcules
Total (without water)70,79716
Polymers69,0632
Non-polymers1,73414
Water362
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
crystal symmetry operation3_555-x,y,-z+1/21
Buried area5550 Å2
ΔGint-79 kcal/mol
Surface area25770 Å2
MethodPISA
Unit cell
Length a, b, c (Å)57.800, 81.860, 140.390
Angle α, β, γ (deg.)90.00, 90.00, 90.00
Int Tables number20
Space group name H-MC2221
Components on special symmetry positions
IDModelComponents
11A-506-

GOL

21A-704-

HOH

-
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: 34531.625 Da / Num. of mol.: 1 / Fragment: unp residues 299-401 / Mutation: R206H
Source method: isolated from a genetically manipulated source
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-SO4 / SULFATE ION


Mass: 96.063 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: SO4
#3: Chemical ChemComp-IYZ / 1-(3-{6-[(CYCLOPROPYLMETHYL)AMINO]IMIDAZO[1,2-B]PYRIDAZIN-3-YL}PHENYL)ETHANONE / IMIDAZOPYRIDAZIN 1


Mass: 306.362 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C18H18N4O
#4: Chemical
ChemComp-GOL / GLYCEROL / GLYCERIN / PROPANE-1,2,3-TRIOL


Mass: 92.094 Da / Num. of mol.: 4 / Source method: obtained synthetically / Formula: C3H8O3
#5: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 124 / 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: 2.4 Å3/Da / Density % sol: 48.85 %
Crystal growTemperature: 293.15 K / Method: vapor diffusion, sitting drop / pH: 6.5
Details: 1.60M MgSO4; 0.1M MES pH 6.5, VAPOR DIFFUSION, SITTING DROP, temperature 293.15K

-
Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: SYNCHROTRON / Site: Diamond / Beamline: I02 / Wavelength: 0.9795 Å
DetectorType: ADSC QUANTUM 315 / Detector: CCD / Date: Feb 4, 2010 / Details: Kirkpatrick Baez bimorph mirror pair
RadiationMonochromator: Si (111) double crystal monochromator / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.9795 Å / Relative weight: 1
ReflectionResolution: 2.42→44.73 Å / Num. all: 13074 / Num. obs: 13046 / % possible obs: 99.8 % / Observed criterion σ(F): 0 / Observed criterion σ(I): 0 / Redundancy: 4.5 % / Biso Wilson estimate: 37.5 Å2 / Rmerge(I) obs: 0.146 / Net I/σ(I): 8.1
Reflection shellResolution: 2.42→2.55 Å / Redundancy: 4.7 % / Rmerge(I) obs: 0.75 / Mean I/σ(I) obs: 2 / Num. unique all: 1858 / % possible all: 100

-
Processing

Software
NameVersionClassification
GDAdata collection
PHASERphasing
REFMAC5.6.0117refinement
MOSFLMdata reduction
SCALAdata scaling
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: pdb entry 3h9r

3h9r


Resolution: 2.42→39.18 Å / Cor.coef. Fo:Fc: 0.933 / Cor.coef. Fo:Fc free: 0.9 / SU B: 22.958 / SU ML: 0.28 / Cross valid method: THROUGHOUT / σ(F): 0 / σ(I): 2 / ESU R: 0.548 / ESU R Free: 0.309 / Stereochemistry target values: MAXIMUM LIKELIHOOD / Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS
RfactorNum. reflection% reflectionSelection details
Rfree0.27922 671 5.1 %RANDOM
Rwork0.21952 ---
all0.271 13046 --
obs0.22268 12375 99.66 %-
Solvent computationIon probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å / Solvent model: MASK
Displacement parametersBiso mean: 35.896 Å2
Baniso -1Baniso -2Baniso -3
1--2.53 Å20 Å20 Å2
2--6.58 Å20 Å2
3----4.05 Å2
Refine analyzeLuzzati coordinate error obs: 0.233 Å
Refinement stepCycle: LAST / Resolution: 2.42→39.18 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms2306 0 57 124 2487
Refine LS restraints
Refine-IDTypeDev idealDev ideal targetNumber
X-RAY DIFFRACTIONr_bond_refined_d0.0120.022413
X-RAY DIFFRACTIONr_bond_other_d0.0010.021603
X-RAY DIFFRACTIONr_angle_refined_deg1.4671.9683278
X-RAY DIFFRACTIONr_angle_other_deg0.7933.0013886
X-RAY DIFFRACTIONr_dihedral_angle_1_deg7.8375292
X-RAY DIFFRACTIONr_dihedral_angle_2_deg37.71323.883103
X-RAY DIFFRACTIONr_dihedral_angle_3_deg16.15815396
X-RAY DIFFRACTIONr_dihedral_angle_4_deg17.5821514
X-RAY DIFFRACTIONr_chiral_restr0.1230.2371
X-RAY DIFFRACTIONr_gen_planes_refined0.0060.0212642
X-RAY DIFFRACTIONr_gen_planes_other0.0010.02487
LS refinement shellResolution: 2.42→2.483 Å / Total num. of bins used: 20
RfactorNum. reflection% reflection
Rfree0.439 33 -
Rwork0.298 849 -
obs--100 %
Refinement TLS params.Method: refined / Origin x: -15.8484 Å / Origin y: -16.5914 Å / Origin z: 17.6326 Å
111213212223313233
T0.1582 Å20.0262 Å20.0028 Å2-0.1164 Å2-0.0194 Å2--0.1506 Å2
L2.5704 °2-0.956 °20.582 °2-1.9489 °2-0.7299 °2--4.5204 °2
S-0.0873 Å °-0.2503 Å °0.0607 Å °0.0924 Å °0.1038 Å °-0.0622 Å °-0.1947 Å °-0.6744 Å °-0.0165 Å °

+
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