[English] 日本語
Yorodumi
- PDB-7c3g: Crystal structure of human ALK2 kinase domain with R206H mutation... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 7c3g
TitleCrystal structure of human ALK2 kinase domain with R206H mutation in complex with a bicyclic pyrazole inhibitor RK-73134
ComponentsActivin receptor type-1
KeywordsSIGNALING PROTEIN / kinase / inhibitor complex
Function / homology
Function and homology information


endocardial cushion cell fate commitment / mitral valve morphogenesis / BMP receptor complex / endocardial cushion fusion / atrial septum primum morphogenesis / BMP receptor activity / cardiac muscle cell fate commitment / acute inflammatory response / activin receptor activity, type I / positive regulation of cardiac epithelial to mesenchymal transition ...endocardial cushion cell fate commitment / mitral valve morphogenesis / BMP receptor complex / endocardial cushion fusion / atrial septum primum morphogenesis / BMP receptor activity / cardiac muscle cell fate commitment / acute inflammatory response / activin receptor activity, type I / positive regulation of cardiac epithelial to mesenchymal transition / activin receptor complex / transforming growth factor beta receptor activity, type I / positive regulation of determination of dorsal identity / endocardial cushion formation / smooth muscle cell differentiation / 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 / embryonic heart tube morphogenesis / transforming growth factor beta binding / gastrulation with mouth forming second / dorsal/ventral pattern formation / determination of left/right symmetry / neural crest cell migration / atrioventricular valve morphogenesis / negative regulation of G1/S transition of mitotic cell cycle / ventricular septum morphogenesis / branching involved in blood vessel morphogenesis / SMAD binding / germ cell development / positive regulation of SMAD protein signal transduction / peptide hormone binding / mesoderm formation / regulation of ossification / BMP signaling pathway / positive regulation of osteoblast differentiation / positive regulation of bone mineralization / negative regulation of signal transduction / protein tyrosine kinase binding / transforming growth factor beta receptor signaling pathway / negative regulation of extrinsic apoptotic signaling pathway / cellular response to growth factor stimulus / positive regulation of peptidyl-tyrosine phosphorylation / apical part of cell / heart development / in utero embryonic development / 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 / Serine/threonine-protein kinase, active site / Serine/Threonine protein kinases active-site signature. ...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 / 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
Similarity search - Domain/homology
Chem-FH0 / Activin receptor type-1
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.802 Å
AuthorsSakai, N. / Mishima-Tsumagari, C. / Matsumoto, T. / Shirouzu, M.
CitationJournal: Bioorg.Med.Chem.Lett. / Year: 2021
Title: Novel bicyclic pyrazoles as potent ALK2 (R206H) inhibitors for the treatment of fibrodysplasia ossificans progressiva.
Authors: Yamamoto, H. / Sakai, N. / Ohte, S. / Sato, T. / Sekimata, K. / Matsumoto, T. / Nakamura, K. / Watanabe, H. / Mishima-Tsumagari, C. / Tanaka, A. / Hashizume, Y. / Honma, T. / Katagiri, T. / ...Authors: Yamamoto, H. / Sakai, N. / Ohte, S. / Sato, T. / Sekimata, K. / Matsumoto, T. / Nakamura, K. / Watanabe, H. / Mishima-Tsumagari, C. / Tanaka, A. / Hashizume, Y. / Honma, T. / Katagiri, T. / Miyazono, K. / Tomoda, H. / Shirouzu, M. / Koyama, H.
History
DepositionMay 12, 2020Deposition site: PDBJ / Processing site: PDBJ
Revision 1.0Mar 3, 2021Provider: repository / Type: Initial release
Revision 1.1Mar 10, 2021Group: Database references / Category: citation / Item: _citation.journal_volume
Revision 1.2Nov 29, 2023Group: Data collection / Database references ...Data collection / Database references / Derived calculations / Refinement description
Category: atom_type / chem_comp_atom ...atom_type / chem_comp_atom / chem_comp_bond / database_2 / pdbx_initial_refinement_model
Item: _atom_type.pdbx_N_electrons / _atom_type.pdbx_scat_Z ..._atom_type.pdbx_N_electrons / _atom_type.pdbx_scat_Z / _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: Activin receptor type-1
hetero molecules


Theoretical massNumber of molelcules
Total (without water)71,88225
Polymers69,0632
Non-polymers2,81823
Water8,449469
1
A: Activin receptor type-1
hetero molecules


Theoretical massNumber of molelcules
Total (without water)35,98913
Polymers34,5321
Non-polymers1,45712
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area500 Å2
ΔGint-36 kcal/mol
Surface area13320 Å2
MethodPISA
2
B: Activin receptor type-1
hetero molecules


Theoretical massNumber of molelcules
Total (without water)35,89312
Polymers34,5321
Non-polymers1,36111
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area0 Å2
ΔGint0 kcal/mol
Surface area13620 Å2
MethodPISA
Unit cell
Length a, b, c (Å)84.340, 140.259, 59.758
Angle α, β, γ (deg.)90.000, 90.000, 90.000
Int Tables number18
Space group name H-MP21212
Components on special symmetry positions
IDModelComponents
11B-769-

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.: 2 / Mutation: R206H
Source method: isolated from a genetically manipulated source
Details: N-terminal 2 residues "SM" are the residual of the purification tag after cleaving off the tag by protease, followed by the Q201 of ALK2
Source: (gene. exp.) Homo sapiens (human) / Gene: ACVR1, ACVRLK2 / Production host: Spodoptera frugiperda (fall armyworm)
References: UniProt: Q04771, receptor protein serine/threonine kinase
#2: Chemical ChemComp-FH0 / ~{N}-[4-(4-methylpiperazin-1-yl)phenyl]-4-(2-pyridin-3-yl-6,7-dihydro-4~{H}-pyrazolo[5,1-c][1,4]oxazin-3-yl)pyrimidin-2-amine


Mass: 468.554 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C26H28N8O / Feature type: SUBJECT OF INVESTIGATION
#3: Chemical
ChemComp-SO4 / SULFATE ION


Mass: 96.063 Da / Num. of mol.: 17 / 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.: 469 / 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: 2.56 Å3/Da / Density % sol: 51.9 %
Crystal growTemperature: 293 K / Method: vapor diffusion, sitting drop
Details: 100 mM HEPES pH 7.6-8.0, 1.5-1.6 M ammonium sulfate
PH range: 7.6 - 8.0

-
Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: SLS / Beamline: X06DA / Wavelength: 1 Å
DetectorType: DECTRIS PILATUS 2M-F / Detector: PIXEL / Date: Sep 5, 2018
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1 Å / Relative weight: 1
ReflectionResolution: 1.8→50 Å / Num. obs: 66091 / % possible obs: 99.7 % / Redundancy: 13.39 % / Biso Wilson estimate: 34.77 Å2 / CC1/2: 1 / Rmerge(I) obs: 0.107 / Rrim(I) all: 0.111 / Net I/σ(I): 18.92
Reflection shellResolution: 1.8→1.91 Å / Redundancy: 13.5 % / Rmerge(I) obs: 1.562 / Mean I/σ(I) obs: 1.6 / Num. unique obs: 10488 / CC1/2: 0.787 / Rrim(I) all: 1.622 / % possible all: 99.1

-
Processing

Software
NameVersionClassification
REFMAC5.8.0257refinement
XDSdata reduction
XDSdata scaling
MOLREPphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 3MTF

3mtf


Resolution: 1.802→46.098 Å / Cor.coef. Fo:Fc: 0.967 / Cor.coef. Fo:Fc free: 0.946 / SU B: 7.048 / SU ML: 0.108 / Cross valid method: FREE R-VALUE / ESU R: 0.122 / ESU R Free: 0.121
Details: Hydrogens have been added in their riding positions
RfactorNum. reflection% reflection
Rfree0.2266 3302 4.997 %
Rwork0.1851 62783 -
all0.187 --
obs-66085 99.622 %
Solvent computationIon probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å / Solvent model: MASK BULK SOLVENT
Displacement parametersBiso mean: 32.697 Å2
Baniso -1Baniso -2Baniso -3
1-1.837 Å20 Å20 Å2
2---2.251 Å20 Å2
3---0.414 Å2
Refinement stepCycle: LAST / Resolution: 1.802→46.098 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms4680 0 171 469 5320
Refine LS restraints
Refine-IDTypeDev idealDev ideal targetNumber
X-RAY DIFFRACTIONr_bond_refined_d0.0140.0134960
X-RAY DIFFRACTIONr_bond_other_d0.0010.0174528
X-RAY DIFFRACTIONr_angle_refined_deg1.841.6496737
X-RAY DIFFRACTIONr_angle_other_deg1.4361.58510473
X-RAY DIFFRACTIONr_dihedral_angle_1_deg7.2425586
X-RAY DIFFRACTIONr_dihedral_angle_2_deg34.79822.048249
X-RAY DIFFRACTIONr_dihedral_angle_3_deg14.37815840
X-RAY DIFFRACTIONr_dihedral_angle_4_deg19.5471532
X-RAY DIFFRACTIONr_chiral_restr0.0920.2628
X-RAY DIFFRACTIONr_gen_planes_refined0.0110.025393
X-RAY DIFFRACTIONr_gen_planes_other0.0010.021047
X-RAY DIFFRACTIONr_nbd_refined0.2120.21043
X-RAY DIFFRACTIONr_symmetry_nbd_other0.1860.24282
X-RAY DIFFRACTIONr_nbtor_refined0.1730.22387
X-RAY DIFFRACTIONr_symmetry_nbtor_other0.0870.22232
X-RAY DIFFRACTIONr_xyhbond_nbd_refined0.1630.2371
X-RAY DIFFRACTIONr_symmetry_nbd_refined0.1160.215
X-RAY DIFFRACTIONr_nbd_other0.1810.257
X-RAY DIFFRACTIONr_symmetry_xyhbond_nbd_refined0.1730.224
X-RAY DIFFRACTIONr_mcbond_it1.9242.3242344
X-RAY DIFFRACTIONr_mcbond_other1.9212.3232343
X-RAY DIFFRACTIONr_mcangle_it2.9143.4672921
X-RAY DIFFRACTIONr_mcangle_other2.9143.4682922
X-RAY DIFFRACTIONr_scbond_it2.7922.7652616
X-RAY DIFFRACTIONr_scbond_other2.4412.6472561
X-RAY DIFFRACTIONr_scangle_it4.2044.033813
X-RAY DIFFRACTIONr_scangle_other3.8933.8573734
X-RAY DIFFRACTIONr_lrange_it7.65628.7175814
X-RAY DIFFRACTIONr_lrange_other7.28228.0365711
LS refinement shell
Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkRefine-ID% reflection obs (%)
1.802-1.8490.3342370.3464532X-RAY DIFFRACTION98.4314
1.849-1.8990.3212330.34429X-RAY DIFFRACTION99.1915
1.899-1.9540.2872290.2694355X-RAY DIFFRACTION99.3068
1.954-2.0140.2552200.2364188X-RAY DIFFRACTION99.4809
2.014-2.080.2752150.2184091X-RAY DIFFRACTION99.5607
2.08-2.1530.2642110.2033995X-RAY DIFFRACTION99.6682
2.153-2.2340.2382000.1883809X-RAY DIFFRACTION99.7264
2.234-2.3250.2251940.1833696X-RAY DIFFRACTION99.8204
2.325-2.4280.2531860.1743547X-RAY DIFFRACTION99.8395
2.428-2.5460.2331800.1723407X-RAY DIFFRACTION99.8886
2.546-2.6840.2241720.1743259X-RAY DIFFRACTION99.9417
2.684-2.8460.2551620.1763092X-RAY DIFFRACTION99.9386
2.846-3.0420.2381530.182901X-RAY DIFFRACTION100
3.042-3.2850.2311430.1942705X-RAY DIFFRACTION100
3.285-3.5970.2111310.1852492X-RAY DIFFRACTION99.9619
3.597-4.0190.1871220.1652303X-RAY DIFFRACTION100
4.019-4.6350.1771060.1372030X-RAY DIFFRACTION100
4.635-5.6650.174920.1411740X-RAY DIFFRACTION100
5.665-7.960.23730.1821373X-RAY DIFFRACTION100
7.96-46.0980.238430.204839X-RAY DIFFRACTION99.7738
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)
10.27350.0485-0.1581.14810.68320.6647-0.0288-0.0555-0.0606-0.19210.0720.0386-0.16580.1241-0.04310.0938-0.05360.03860.0495-0.00790.0957-18.987118.788229.0232
20.08470.31490.04721.5987-0.1320.330.06040.04050.03320.28510.04230.22190.0210.0727-0.10270.0762-0.00180.01160.05780.00980.0881-17.754853.04861.9413
Refinement TLS group
IDRefine-IDRefine TLS-IDSelectionAuth asym-IDAuth seq-ID
1X-RAY DIFFRACTION1ALLA203 - 499
2X-RAY DIFFRACTION2ALLB204 - 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