[English] 日本語
Yorodumi
- PDB-4c02: Crystal structure of human ACVR1 (ALK2) in complex with FKBP12.6 ... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 4c02
TitleCrystal structure of human ACVR1 (ALK2) in complex with FKBP12.6 and dorsomorphin
Components
  • ACTIVIN RECEPTOR TYPE-1
  • PEPTIDYL-PROLYL CIS-TRANS ISOMERASE FKBP1B
KeywordsTRANSFERASE/ISOMERASE / TRANSFERASE-ISOMERASE COMPLEX / TRANSFERASE / DORSOMORPHIN
Function / homology
Function and homology information


endocardial cushion cell fate commitment / mitral valve morphogenesis / atrial septum primum morphogenesis / endocardial cushion fusion / BMP receptor complex / BMP receptor activity / cardiac muscle cell fate commitment / activin receptor activity, type I / positive regulation of cardiac epithelial to mesenchymal transition / positive regulation of determination of dorsal identity ...endocardial cushion cell fate commitment / mitral valve morphogenesis / atrial septum primum morphogenesis / endocardial cushion fusion / BMP receptor complex / BMP receptor activity / cardiac muscle cell fate commitment / activin receptor activity, type I / positive regulation of cardiac epithelial to mesenchymal transition / positive regulation of determination of dorsal identity / acute inflammatory response / transforming growth factor beta receptor activity, type I / activin receptor complex / smooth muscle cell differentiation / endocardial cushion formation / receptor protein serine/threonine kinase / transmembrane receptor protein serine/threonine kinase activity / pharyngeal system development / activin binding / cellular response to BMP stimulus / activin receptor signaling pathway / negative regulation of activin receptor signaling pathway / positive regulation of sequestering of calcium ion / cyclic nucleotide binding / transforming growth factor beta binding / embryonic heart tube morphogenesis / negative regulation of release of sequestered calcium ion into cytosol / negative regulation of insulin secretion involved in cellular response to glucose stimulus / gastrulation with mouth forming second / dorsal/ventral pattern formation / neuronal action potential propagation / insulin secretion involved in cellular response to glucose stimulus / determination of left/right symmetry / neural crest cell migration / cell communication by electrical coupling involved in cardiac conduction / response to redox state / atrioventricular valve morphogenesis / protein maturation by protein folding / 'de novo' protein folding / negative regulation of heart rate / branching involved in blood vessel morphogenesis / negative regulation of G1/S transition of mitotic cell cycle / negative regulation of phosphoprotein phosphatase activity / FK506 binding / ventricular septum morphogenesis / positive regulation of axon regeneration / SMAD binding / germ cell development / peptide hormone binding / positive regulation of SMAD protein signal transduction / : / mesoderm formation / smooth muscle contraction / negative regulation of ryanodine-sensitive calcium-release channel activity / regulation of ossification / response to vitamin E / calcium channel inhibitor activity / regulation of cardiac muscle contraction by regulation of the release of sequestered calcium ion / positive regulation of osteoblast differentiation / BMP signaling pathway / positive regulation of bone mineralization / protein peptidyl-prolyl isomerization / T cell proliferation / negative regulation of signal transduction / regulation of release of sequestered calcium ion into cytosol by sarcoplasmic reticulum / release of sequestered calcium ion into cytosol / regulation of ryanodine-sensitive calcium-release channel activity / Ion homeostasis / sarcoplasmic reticulum membrane / calcium channel complex / protein tyrosine kinase binding / regulation of cytosolic calcium ion concentration / transforming growth factor beta receptor signaling pathway / peptidylprolyl isomerase / peptidyl-prolyl cis-trans isomerase activity / negative regulation of extrinsic apoptotic signaling pathway / response to hydrogen peroxide / Stimuli-sensing channels / cellular response to growth factor stimulus / Z disc / positive regulation of peptidyl-tyrosine phosphorylation / apical part of cell / heart development / positive regulation of cytosolic calcium ion concentration / protein refolding / in utero embryonic development / transmembrane transporter binding / protein kinase activity / positive regulation of cell migration / cadherin binding / phosphorylation / signaling receptor 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 / membrane / 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 / 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
CITRATE ANION / Chem-TAK / Peptidyl-prolyl cis-trans isomerase FKBP1B / Activin receptor type-1
Similarity search - Component
Biological speciesHOMO SAPIENS (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.17 Å
AuthorsWilliams, E. / Riesebos, E. / Vollmar, M. / Krojer, T. / Bradley, A. / Shrestha, L. / Kupinska, K. / von Delft, F. / Arrowsmith, C.H. / Edwards, A.M. ...Williams, E. / Riesebos, E. / Vollmar, M. / Krojer, T. / Bradley, A. / Shrestha, L. / Kupinska, K. / von Delft, F. / Arrowsmith, C.H. / Edwards, A.M. / Bountra, C. / Bullock, A.
CitationJournal: Ph D Thesis
Title: Crystal Structure of Human Acvr1 (Alk2) in Complex with Fkbp12.6 And Dorsomorphin
Authors: Williams, E. / Riesebos, E. / Vollmar, M. / Krojer, T. / Bradley, A. / Shrestha, L. / Kupinska, K. / von Delft, F. / Arrowsmith, C.H. / Edwards, A.M. / Bountra, C. / Bullock, A.
History
DepositionJul 31, 2013Deposition site: PDBE / Processing site: PDBE
Revision 1.0Aug 7, 2013Provider: repository / Type: Initial release
Revision 1.1Jan 24, 2018Group: Database references / Category: citation_author / Item: _citation_author.name
Revision 2.0Feb 10, 2021Group: Advisory / Atomic model ...Advisory / Atomic model / Data collection / Database references / Derived calculations / Other / Structure summary
Category: atom_site / atom_site_anisotrop ...atom_site / atom_site_anisotrop / pdbx_database_status / pdbx_poly_seq_scheme / pdbx_struct_sheet_hbond / pdbx_unobs_or_zero_occ_atoms / pdbx_validate_torsion / struct_conf / struct_ref_seq / struct_sheet_range / struct_site / struct_site_gen
Item: _atom_site.auth_seq_id / _atom_site_anisotrop.pdbx_auth_seq_id ..._atom_site.auth_seq_id / _atom_site_anisotrop.pdbx_auth_seq_id / _pdbx_database_status.status_code_sf / _pdbx_poly_seq_scheme.pdb_seq_num / _pdbx_struct_sheet_hbond.range_1_auth_seq_id / _pdbx_struct_sheet_hbond.range_2_auth_seq_id / _pdbx_unobs_or_zero_occ_atoms.auth_seq_id / _pdbx_validate_torsion.auth_seq_id / _struct_conf.beg_auth_seq_id / _struct_conf.end_auth_seq_id / _struct_ref_seq.pdbx_auth_seq_align_beg / _struct_ref_seq.pdbx_auth_seq_align_end / _struct_sheet_range.beg_auth_seq_id / _struct_sheet_range.end_auth_seq_id / _struct_site.pdbx_auth_asym_id / _struct_site.pdbx_auth_comp_id / _struct_site.pdbx_auth_seq_id / _struct_site_gen.auth_seq_id
Revision 2.1Dec 20, 2023Group: 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 FKBP1B
hetero molecules


Theoretical massNumber of molelcules
Total (without water)51,91624
Polymers49,1972
Non-polymers2,71922
Water4,161231
1


  • Idetical with deposited unit
  • defined by author&software
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area7250 Å2
ΔGint23.4 kcal/mol
Surface area18780 Å2
MethodPISA
Unit cell
Length a, b, c (Å)182.330, 182.330, 182.330
Angle α, β, γ (deg.)90.00, 90.00, 90.00
Int Tables number213
Space group name H-MP4132

-
Components

-
Protein , 2 types, 2 molecules AB

#1: Protein ACTIVIN RECEPTOR TYPE-1 / ACTIVIN RECEPTOR TYPE I / ACTR-I / ACTIVIN RECEPTOR-LIKE KINA SE 2 / ALK-2 / SERINE/THREONINE- ...ACTIVIN RECEPTOR TYPE I / ACTR-I / ACTIVIN RECEPTOR-LIKE KINA SE 2 / ALK-2 / SERINE/THREONINE-PROTEIN KINASE RECEPTOR R1 / SKR1 / TG F-B SUPERFAMILY RECEPTOR TYPE I / TSR-I / ACVR1A


Mass: 37398.746 Da / Num. of mol.: 1 / Fragment: KINASE DOMAIN, RESIDUES 172-499
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) HOMO SAPIENS (human) / Plasmid: PFB-LIC-BSE / Production host: SPODOPTERA FRUGIPERDA (fall armyworm) / Strain (production host): SF9
References: UniProt: Q04771, non-specific protein-tyrosine kinase, receptor protein serine/threonine kinase
#2: Protein PEPTIDYL-PROLYL CIS-TRANS ISOMERASE FKBP1B / PPIASE FKBP1B / 12.6 KDA FK506-BINDING PROTEIN / 12.6 KDA FKB P / FKBP-12.6 / FK506-BINDING PROTEIN ...PPIASE FKBP1B / 12.6 KDA FK506-BINDING PROTEIN / 12.6 KDA FKB P / FKBP-12.6 / FK506-BINDING PROTEIN 1B / FKBP-1B / IMMUNOPHILIN FKBP 12.6 / ROTAMASE / H-FKBP-12 / FKBP1B


Mass: 11798.501 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) HOMO SAPIENS (human) / Plasmid: PNIC28-BSA4 / Production host: ESCHERICHIA COLI (E. coli) / Strain (production host): BL21(DE3) / Variant (production host): ROSETTA PLYSS / References: UniProt: P68106, peptidylprolyl isomerase

-
Non-polymers , 4 types, 253 molecules

#3: Chemical
ChemComp-FLC / CITRATE ANION / Citric acid


Mass: 189.100 Da / Num. of mol.: 8 / Source method: obtained synthetically / Formula: C6H5O7
#4: Chemical ChemComp-TAK / 6-[4-(2-piperidin-1-ylethoxy)phenyl]-3-pyridin-4-ylpyrazolo[1,5-a]pyrimidine / Dorsomorphin


Mass: 399.488 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C24H25N5O
#5: Chemical
ChemComp-EDO / 1,2-ETHANEDIOL / ETHYLENE GLYCOL / Ethylene glycol


Mass: 62.068 Da / Num. of mol.: 13 / Source method: obtained synthetically / Formula: C2H6O2
#6: Water ChemComp-HOH / water / Water


Mass: 18.015 Da / Num. of mol.: 231 / Source method: isolated from a natural source / Formula: H2O

-
Details

Sequence detailsN TERMINAL METHIONINE (RESIDUE 0) SEEN PRIOR TO RESIDUE 1 (GLY).

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 5.11 Å3/Da / Density % sol: 75.95 % / Description: NONE
Crystal growpH: 7.2 / Details: 1.8M AMMONIUM CITRATE, pH 7.2

-
Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: SYNCHROTRON / Site: Diamond / Beamline: I04 / Wavelength: 0.9686
DetectorType: DECTRIS PILATUS 6M / Detector: PIXEL / Date: Jun 22, 2013
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.9686 Å / Relative weight: 1
ReflectionResolution: 2.17→40 Å / Num. obs: 169113 / % possible obs: 99.9 % / Observed criterion σ(I): 2 / Redundancy: 9 % / Rmerge(I) obs: 0.17 / Net I/σ(I): 8
Reflection shellResolution: 2.17→2.23 Å / Redundancy: 9.3 % / Rmerge(I) obs: 1.07 / Mean I/σ(I) obs: 2 / % possible all: 100

-
Processing

Software
NameVersionClassification
REFMAC5.7.0032refinement
MOSFLMdata reduction
Aimlessdata scaling
PHASERphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: PDB ENTRIES 1C9H AND 3H9R

1c9h

3h9r


Resolution: 2.17→39.82 Å / Cor.coef. Fo:Fc: 0.957 / Cor.coef. Fo:Fc free: 0.949 / SU B: 6.385 / SU ML: 0.084 / Cross valid method: THROUGHOUT / ESU R: 0.125 / ESU R Free: 0.117 / Stereochemistry target values: MAXIMUM LIKELIHOOD
Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS.U VALUES WITH TLS ADDED DISORDERED REGIONS WERE NOT MODELED AND RELEVANT LOOPS DELETED FROM STRUCTURE.
RfactorNum. reflection% reflectionSelection details
Rfree0.19754 2787 5.1 %RANDOM
Rwork0.17729 ---
obs0.17833 52159 99.75 %-
Solvent computationIon probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å / Solvent model: MASK
Displacement parametersBiso mean: 36.836 Å2
Baniso -1Baniso -2Baniso -3
1-0 Å20 Å20 Å2
2--0 Å20 Å2
3---0 Å2
Refinement stepCycle: LAST / Resolution: 2.17→39.82 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms3271 0 179 231 3681
Refine LS restraints
Refine-IDTypeDev idealDev ideal targetNumber
X-RAY DIFFRACTIONr_bond_refined_d0.0120.0193589
X-RAY DIFFRACTIONr_bond_other_d0.0010.023380
X-RAY DIFFRACTIONr_angle_refined_deg1.7671.9994865
X-RAY DIFFRACTIONr_angle_other_deg0.77737761
X-RAY DIFFRACTIONr_dihedral_angle_1_deg6.3495442
X-RAY DIFFRACTIONr_dihedral_angle_2_deg36.91923.851148
X-RAY DIFFRACTIONr_dihedral_angle_3_deg13.79615583
X-RAY DIFFRACTIONr_dihedral_angle_4_deg19.4351522
X-RAY DIFFRACTIONr_chiral_restr0.1570.2538
X-RAY DIFFRACTIONr_gen_planes_refined0.0060.0214019
X-RAY DIFFRACTIONr_gen_planes_other0.0010.02802
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_it4.7065.2371717
X-RAY DIFFRACTIONr_mcbond_other4.7075.2351716
X-RAY DIFFRACTIONr_mcangle_it6.5529.6792149
X-RAY DIFFRACTIONr_mcangle_other
X-RAY DIFFRACTIONr_scbond_it6.8386.3351872
X-RAY DIFFRACTIONr_scbond_other
X-RAY DIFFRACTIONr_scangle_it
X-RAY DIFFRACTIONr_scangle_other
X-RAY DIFFRACTIONr_long_range_B_refined
X-RAY DIFFRACTIONr_long_range_B_other
X-RAY DIFFRACTIONr_rigid_bond_restr
X-RAY DIFFRACTIONr_sphericity_free
X-RAY DIFFRACTIONr_sphericity_bonded
LS refinement shellResolution: 2.17→2.227 Å / Total num. of bins used: 20
RfactorNum. reflection% reflection
Rfree0.3 194 -
Rwork0.276 3794 -
obs--99.97 %
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)
10.3214-0.0833-0.20060.16720.05910.5855-0.07070.00340.0361-0.01440.02240.0410.01060.08730.04830.0972-0.0132-0.00910.07960.01490.0353-50.99316.1065.1011
21.1255-0.0583-1.01881.4998-0.47631.1139-0.00930.07590.30580.06690.36480.23140.0013-0.1909-0.35550.04150.0350.02630.10430.08970.1408-82.681218.845321.2804
Refinement TLS group
IDRefine-IDRefine TLS-IDAuth asym-IDAuth seq-ID
1X-RAY DIFFRACTION1A178 - 192
2X-RAY DIFFRACTION1A193 - 257
3X-RAY DIFFRACTION1A258 - 296
4X-RAY DIFFRACTION1A297 - 333
5X-RAY DIFFRACTION1A334 - 381
6X-RAY DIFFRACTION1A384 - 499
7X-RAY DIFFRACTION2B1 - 6
8X-RAY DIFFRACTION2B7 - 33
9X-RAY DIFFRACTION2B34 - 47
10X-RAY DIFFRACTION2B48 - 54
11X-RAY DIFFRACTION2B55 - 107

+
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