[English] 日本語
Yorodumi
- PDB-6i1s: Crystal structure of the ACVR1 (ALK2) kinase in complex with FKBP... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 6i1s
TitleCrystal structure of the ACVR1 (ALK2) kinase in complex with FKBP12 and the inhibitor E6201
Components
  • Activin receptor type-1
  • Peptidyl-prolyl cis-trans isomerase FKBP1A
KeywordsSIGNALING PROTEIN / Kinase / Inhibitor / ALK2 / ACVR1 / FKBP12 / Complex
Function / homology
Function and homology information


endocardial cushion cell fate commitment / mitral valve morphogenesis / endocardial cushion fusion / BMP receptor complex / atrial septum primum morphogenesis / macrolide binding / BMP receptor activity / cardiac muscle cell fate commitment / acute inflammatory response / activin receptor binding ...endocardial cushion cell fate commitment / mitral valve morphogenesis / endocardial cushion fusion / BMP receptor complex / atrial septum primum morphogenesis / macrolide binding / BMP receptor activity / cardiac muscle cell fate commitment / acute inflammatory response / activin receptor binding / activin receptor activity, type I / positive regulation of cardiac epithelial to mesenchymal transition / cytoplasmic side of membrane / positive regulation of determination of dorsal identity / transforming growth factor beta receptor activity, type I / activin receptor complex / endocardial cushion formation / smooth muscle cell differentiation / signaling receptor inhibitor activity / transforming growth factor beta receptor binding / TGFBR1 LBD Mutants in Cancer / receptor protein serine/threonine kinase / transmembrane receptor protein serine/threonine kinase activity / pharyngeal system development / activin binding / type I transforming growth factor beta receptor binding / cellular response to BMP stimulus / activin receptor signaling pathway / negative regulation of activin receptor signaling pathway / heart trabecula formation / transforming growth factor beta binding / embryonic heart tube morphogenesis / terminal cisterna / ryanodine receptor complex / gastrulation with mouth forming second / I-SMAD binding / dorsal/ventral pattern formation / regulation of amyloid precursor protein catabolic process / determination of left/right symmetry / neural crest cell migration / atrioventricular valve morphogenesis / protein maturation by protein folding / ventricular cardiac muscle tissue morphogenesis / 'de novo' protein folding / branching involved in blood vessel morphogenesis / negative regulation of G1/S transition of mitotic cell cycle / negative regulation of phosphoprotein phosphatase activity / ventricular septum morphogenesis / FK506 binding / SMAD binding / mTORC1-mediated signalling / TGF-beta receptor signaling activates SMADs / germ cell development / peptide hormone binding / positive regulation of SMAD protein signal transduction / Calcineurin activates NFAT / mesoderm formation / regulation of immune response / regulation of ossification / BMP signaling pathway / positive regulation of bone mineralization / positive regulation of osteoblast differentiation / protein peptidyl-prolyl isomerization / negative regulation of signal transduction / heart morphogenesis / supramolecular fiber organization / regulation of ryanodine-sensitive calcium-release channel activity / sarcoplasmic reticulum membrane / T cell activation / transforming growth factor beta receptor signaling pathway / protein tyrosine kinase binding / TGF-beta receptor signaling in EMT (epithelial to mesenchymal transition) / peptidylprolyl isomerase / sarcoplasmic reticulum / peptidyl-prolyl cis-trans isomerase activity / negative regulation of extrinsic apoptotic signaling pathway / calcium ion transmembrane transport / negative regulation of transforming growth factor beta receptor signaling pathway / cellular response to growth factor stimulus / Z disc / SARS-CoV-1 activates/modulates innate immune responses / regulation of protein localization / positive regulation of peptidyl-tyrosine phosphorylation / protein folding / positive regulation of protein binding / apical part of cell / heart development / protein refolding / positive regulation of canonical NF-kappaB signal transduction / in utero embryonic development / transmembrane transporter binding / amyloid fibril formation / Potential therapeutics for SARS / protein kinase activity / positive regulation of cell migration / cadherin binding / phosphorylation / protein serine/threonine kinase activity / positive regulation of DNA-templated transcription / protein homodimerization activity
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 / Chitinase A; domain 3 - #40 / Snake toxin-like superfamily / Chitinase A; domain 3 ...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 / Chitinase A; domain 3 - #40 / Snake toxin-like superfamily / Chitinase A; domain 3 / FKBP-type peptidyl-prolyl cis-trans isomerase domain profile. / FKBP-type peptidyl-prolyl cis-trans isomerase domain / FKBP-type peptidyl-prolyl cis-trans isomerase / Peptidyl-prolyl cis-trans isomerase domain superfamily / Protein tyrosine and serine/threonine kinase / Serine-threonine/tyrosine-protein kinase, catalytic domain / 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. / Serine/Threonine protein kinases, catalytic domain / Roll / 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-E26 / Peptidyl-prolyl cis-trans isomerase FKBP1A / Activin receptor type-1
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.52 Å
AuthorsWilliams, E.P. / Pinkas, D.M. / Fortin, J. / Newman, J.A. / Bradshaw, W.J. / Mahajan, P. / Kupinska, K. / Burgess-Brown, N. / von Delft, F. / Arrowsmith, C.H. ...Williams, E.P. / Pinkas, D.M. / Fortin, J. / Newman, J.A. / Bradshaw, W.J. / Mahajan, P. / Kupinska, K. / Burgess-Brown, N. / von Delft, F. / Arrowsmith, C.H. / Edwards, A.M. / Bountra, C. / Bullock, A.N.
CitationJournal: Cancer Cell / Year: 2020
Title: Mutant ACVR1 Arrests Glial Cell Differentiation to Drive Tumorigenesis in Pediatric Gliomas.
Authors: Fortin, J. / Tian, R. / Zarrabi, I. / Hill, G. / Williams, E. / Sanchez-Duffhues, G. / Thorikay, M. / Ramachandran, P. / Siddaway, R. / Wong, J.F. / Wu, A. / Apuzzo, L.N. / Haight, J. / You- ...Authors: Fortin, J. / Tian, R. / Zarrabi, I. / Hill, G. / Williams, E. / Sanchez-Duffhues, G. / Thorikay, M. / Ramachandran, P. / Siddaway, R. / Wong, J.F. / Wu, A. / Apuzzo, L.N. / Haight, J. / You-Ten, A. / Snow, B.E. / Wakeham, A. / Goldhamer, D.J. / Schramek, D. / Bullock, A.N. / Dijke, P.T. / Hawkins, C. / Mak, T.W.
History
DepositionOct 30, 2018Deposition site: PDBE / Processing site: PDBE
Revision 1.0Sep 11, 2019Provider: repository / Type: Initial release
Revision 1.1Mar 25, 2020Group: Database references / Category: citation / citation_author
Item: _citation.country / _citation.journal_abbrev ..._citation.country / _citation.journal_abbrev / _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
Revision 1.2Jan 24, 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
B: Peptidyl-prolyl cis-trans isomerase FKBP1A
hetero molecules


Theoretical massNumber of molelcules
Total (without water)50,47012
Polymers49,4542
Non-polymers1,01610
Water4,270237
1


  • Idetical with deposited unit
  • defined by author&software
  • Evidence: gel filtration, Each protein was individually verified by intact Mass Spec and the complex was purified by gel filtration and analysed by SDS PAGE. Comparison to single protein elution ...Evidence: gel filtration, Each protein was individually verified by intact Mass Spec and the complex was purified by gel filtration and analysed by SDS PAGE. Comparison to single protein elution profiles showed a peak shift in the gel filtration profile that confirms complex formation.
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area3580 Å2
ΔGint-20 kcal/mol
Surface area19000 Å2
MethodPISA
Unit cell
Length a, b, c (Å)44.309, 108.599, 114.389
Angle α, β, γ (deg.)90.000, 90.000, 90.000
Int Tables number19
Space group name H-MP212121
Space group name HallP2ac2ab
Symmetry operation#1: x,y,z
#2: x+1/2,-y+1/2,-z
#3: -x,y+1/2,-z+1/2
#4: -x+1/2,-y,z+1/2

-
Components

-
Protein , 2 types, 2 molecules AB

#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: 37398.746 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Details: Standard peptide protein chain. / Source: (gene. exp.) Homo sapiens (human) / Gene: ACVR1, ACVRLK2 / Production host: Spodoptera frugiperda (fall armyworm) / Variant (production host): Sf9
References: UniProt: Q04771, receptor protein serine/threonine kinase
#2: Protein Peptidyl-prolyl cis-trans isomerase FKBP1A / PPIase FKBP1A / 12 kDa FK506-binding protein / FKBP-12 / Calstabin-1 / FK506-binding protein 1A / ...PPIase FKBP1A / 12 kDa FK506-binding protein / FKBP-12 / Calstabin-1 / FK506-binding protein 1A / FKBP-1A / Immunophilin FKBP12 / Rotamase


Mass: 12054.782 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Details: Standard polypetide protein chain. / Source: (gene. exp.) Homo sapiens (human) / Gene: FKBP1A, FKBP1, FKBP12 / Plasmid: pNIC28-Bsa4 / Production host: Escherichia coli BL21(DE3) (bacteria) / References: UniProt: P62942, peptidylprolyl isomerase

-
Non-polymers , 4 types, 247 molecules

#3: Chemical ChemComp-E26 / (4~{S},5~{R},6~{Z},9~{S},10~{S},12~{E})-16-(ethylamino)-4,5-dimethyl-9,10,18-tris(oxidanyl)-3-oxabicyclo[12.4.0]octadeca-1(14),6,12,15,17-pentaene-2,8-dione


Mass: 389.442 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C21H27NO6 / Feature type: SUBJECT OF INVESTIGATION
#4: Chemical
ChemComp-EDO / 1,2-ETHANEDIOL / ETHYLENE GLYCOL


Mass: 62.068 Da / Num. of mol.: 7 / Source method: obtained synthetically / Formula: C2H6O2
#5: Chemical ChemComp-SO4 / SULFATE ION


Mass: 96.063 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: SO4
#6: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 237 / 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: 2.79 Å3/Da / Density % sol: 55.88 % / Description: Clear crystal. Oblong.
Crystal growTemperature: 277 K / Method: vapor diffusion, sitting drop / pH: 6.5
Details: 0.05M ammonium sulfate, 30% pentaerythritol ethoxylate 15/4, 0.1M bis-tris pH 6.5

-
Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: Diamond / Beamline: I03 / Wavelength: 0.9763 Å
DetectorType: ADSC QUANTUM 315 / Detector: CCD / Date: May 4, 2018
RadiationMonochromator: Double Crystal / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.9763 Å / Relative weight: 1
ReflectionResolution: 1.52→41.32 Å / Num. obs: 85856 / % possible obs: 100 % / Observed criterion σ(F): 2 / Redundancy: 5.8 % / Biso Wilson estimate: 15.41 Å2 / CC1/2: 0.998 / Rmerge(I) obs: 0.074 / Rpim(I) all: 0.05 / Rrim(I) all: 0.089 / Net I/σ(I): 11.5
Reflection shellResolution: 1.52→1.55 Å / Redundancy: 5.8 % / Rmerge(I) obs: 0.98 / Mean I/σ(I) obs: 2 / Num. unique obs: 4196 / CC1/2: 0.635 / Rpim(I) all: 0.665 / Rrim(I) all: 1.19 / Χ2: 0.83 / % possible all: 99.9

-
Processing

Software
NameVersionClassification
PHENIX1.13-2998refinement
iMOSFLM7.2.2data reduction
Aimless7.0.044data scaling
PHASER7.0.044phasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 3H9R

3h9r


Resolution: 1.52→41.31 Å / Cross valid method: FREE R-VALUE / σ(F): 2
RfactorNum. reflection% reflectionSelection details
Rfree0.1927 4149 4.89 %Random selection
Rwork0.1767 ---
obs0.1775 85764 99.96 %-
Solvent computationVDW probe radii: 1.11 Å
Displacement parametersBiso mean: 17.43 Å2
Refinement stepCycle: LAST / Resolution: 1.52→41.31 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms3363 0 66 237 3666

+
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://pdbjlvh1.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