[English] 日本語
Yorodumi
- PDB-8bzi: Human MST3 (STK24) kinase in complex with inhibitor MR39 -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 8bzi
TitleHuman MST3 (STK24) kinase in complex with inhibitor MR39
ComponentsSerine/threonine-protein kinase 24
KeywordsTRANSFERASE / selective kinase inhibitors / structure-based drug design
Function / homology
Function and homology information


Apoptotic execution phase / FAR/SIN/STRIPAK complex / regulation of axon regeneration / intrinsic apoptotic signaling pathway in response to oxidative stress / execution phase of apoptosis / Apoptotic cleavage of cellular proteins / negative regulation of cell migration / cellular response to starvation / protein autophosphorylation / cellular response to oxidative stress ...Apoptotic execution phase / FAR/SIN/STRIPAK complex / regulation of axon regeneration / intrinsic apoptotic signaling pathway in response to oxidative stress / execution phase of apoptosis / Apoptotic cleavage of cellular proteins / negative regulation of cell migration / cellular response to starvation / protein autophosphorylation / cellular response to oxidative stress / protein phosphorylation / non-specific serine/threonine protein kinase / protein kinase activity / intracellular signal transduction / cadherin binding / protein serine kinase activity / protein serine/threonine kinase activity / nucleolus / Golgi apparatus / signal transduction / extracellular exosome / nucleoplasm / ATP binding / metal ion binding / nucleus / membrane / cytoplasm / cytosol
Similarity search - Function
Programmed cell death protein 10, dimerisation domain superfamily / : / Programmed cell death protein 10, dimerisation domain / : / 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-SJL / Serine/threonine-protein kinase 24
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.72 Å
AuthorsBalourdas, D.I. / Rak, M. / Tesch, R. / Knapp, S. / Joerger, A.C. / Structural Genomics Consortium (SGC)
Funding support Germany, 1items
OrganizationGrant numberCountry
German Research Foundation (DFG)JO 1473/1-3 Germany
CitationJournal: Eur.J.Med.Chem. / Year: 2023
Title: Shifting the selectivity of pyrido[2,3-d]pyrimidin-7(8H)-one inhibitors towards the salt-inducible kinase (SIK) subfamily.
Authors: Rak, M. / Tesch, R. / Berger, L.M. / Shevchenko, E. / Raab, M. / Tjaden, A. / Zhubi, R. / Balourdas, D.I. / Joerger, A.C. / Poso, A. / Kramer, A. / Elson, L. / Lucic, A. / Kronenberger, T. / ...Authors: Rak, M. / Tesch, R. / Berger, L.M. / Shevchenko, E. / Raab, M. / Tjaden, A. / Zhubi, R. / Balourdas, D.I. / Joerger, A.C. / Poso, A. / Kramer, A. / Elson, L. / Lucic, A. / Kronenberger, T. / Hanke, T. / Strebhardt, K. / Sanhaji, M. / Knapp, S.
History
DepositionDec 14, 2022Deposition site: PDBE / Processing site: PDBE
Revision 1.0Jan 18, 2023Provider: repository / Type: Initial release
Revision 2.0May 24, 2023Group: Non-polymer description / Category: chem_comp / Item: _chem_comp.formula
Revision 2.1Aug 2, 2023Group: Database references / Category: citation / citation_author
Item: _citation.country / _citation.journal_abbrev ..._citation.country / _citation.journal_abbrev / _citation.journal_id_ASTM / _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 2.2Feb 7, 2024Group: Data collection / Refinement description
Category: chem_comp_atom / chem_comp_bond / pdbx_initial_refinement_model
Item: _pdbx_initial_refinement_model.accession_code / _pdbx_initial_refinement_model.source_name

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Serine/threonine-protein kinase 24
hetero molecules


Theoretical massNumber of molelcules
Total (without water)35,1965
Polymers34,5601
Non-polymers6374
Water3,981221
1


  • Idetical with deposited unit
  • defined by author&software
  • Evidence: gel filtration
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area560 Å2
ΔGint9 kcal/mol
Surface area12770 Å2
MethodPISA
Unit cell
Length a, b, c (Å)98.788, 58.749, 61.465
Angle α, β, γ (deg.)90.000, 93.051, 90.000
Int Tables number5
Space group name H-MC121
Space group name HallC2y

-
Components

#1: Protein Serine/threonine-protein kinase 24 / Mammalian STE20-like protein kinase 3 / MST-3 / STE20-like kinase MST3


Mass: 34559.648 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: STK24, MST3, STK3 / Production host: Escherichia coli (E. coli)
References: UniProt: Q9Y6E0, non-specific serine/threonine protein kinase
#2: Chemical ChemComp-SJL / 8-(4-azanylbutyl)-6-[2,5-bis(fluoranyl)-4-(6-methylpyridin-2-yl)phenyl]-2-(methylamino)pyrido[2,3-d]pyrimidin-7-one


Mass: 450.484 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C24H24F2N6O / Feature type: SUBJECT OF INVESTIGATION
#3: Chemical ChemComp-EDO / 1,2-ETHANEDIOL / ETHYLENE GLYCOL


Mass: 62.068 Da / Num. of mol.: 3 / Source method: obtained synthetically / Formula: C2H6O2
#4: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 221 / 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: 2.58 Å3/Da / Density % sol: 52.27 %
Crystal growTemperature: 293 K / Method: vapor diffusion, sitting drop
Details: Protein solution: 11 mg/mL MST3 in 25 mM HEPES pH 7.5, 200 mM NaCl, 0.5 mM TCEP, 5% glycerol, with 1 mM inhibitor). Crystallization buffer: 20% PEG 3350, 0.1 M bis-tris pH 6.5.

-
Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: SLS / Beamline: X06SA / Wavelength: 0.99999 Å
DetectorType: DECTRIS EIGER X 16M / Detector: PIXEL / Date: Sep 5, 2022
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.99999 Å / Relative weight: 1
ReflectionResolution: 1.72→39.52 Å / Num. obs: 36820 / % possible obs: 98.4 % / Redundancy: 6.9 % / Biso Wilson estimate: 30.2449699539 Å2 / CC1/2: 0.999 / Rmerge(I) obs: 0.042 / Net I/σ(I): 18.4
Reflection shellResolution: 1.72→1.75 Å / Mean I/σ(I) obs: 2.2 / Num. unique obs: 1919 / CC1/2: 0.811

-
Processing

Software
NameVersionClassification
PHENIX1.10.1_2155refinement
XDSdata reduction
Aimlessdata scaling
PHASERphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 7B32

7b32


Resolution: 1.72→39.5 Å / SU ML: 0.180103877902 / Cross valid method: FREE R-VALUE / σ(F): 1.34596706024 / Phase error: 19.6147524922
Stereochemistry target values: GeoStd + Monomer Library + CDL v1.2
RfactorNum. reflection% reflection
Rfree0.195790856793 1809 4.91389145434 %
Rwork0.15183354662 35005 -
obs0.153963122918 36814 98.2650010677 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL
Displacement parametersBiso mean: 37.2487699881 Å2
Refinement stepCycle: LAST / Resolution: 1.72→39.5 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms2075 0 45 221 2341
Refine LS restraints
Refine-IDTypeDev idealNumber
X-RAY DIFFRACTIONf_bond_d0.006844497355722202
X-RAY DIFFRACTIONf_angle_d0.8289637255532988
X-RAY DIFFRACTIONf_chiral_restr0.0526309227401330
X-RAY DIFFRACTIONf_plane_restr0.0052820427303434
X-RAY DIFFRACTIONf_dihedral_angle_d12.81672170921347
LS refinement shell
Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkRefine-ID% reflection obs (%)
1.72-1.76650.2746156414381420.2192496816142629X-RAY DIFFRACTION97.2280701754
1.7665-1.81850.2478044858321490.1908758034462688X-RAY DIFFRACTION98.988136776
1.8185-1.87720.2291131722641430.1779496491862690X-RAY DIFFRACTION98.6764193661
1.8772-1.94430.236334111971620.169601598952670X-RAY DIFFRACTION98.8481675393
1.9443-2.02210.2301163091631700.1469414962162677X-RAY DIFFRACTION98.8541666667
2.0221-2.11420.1822932448041310.1408665689432693X-RAY DIFFRACTION99.0182328191
2.1142-2.22560.165473689081080.1423564714532724X-RAY DIFFRACTION98.8826815642
2.2256-2.3650.1938019263041200.1405757208772700X-RAY DIFFRACTION97.1743625086
2.365-2.54760.2360178986511210.1544518811842615X-RAY DIFFRACTION95.5640936081
2.5476-2.80390.2107707830361340.1663455905722732X-RAY DIFFRACTION99.306999307
2.8039-3.20950.1893532759341530.1645953117832720X-RAY DIFFRACTION99.2743607464
3.2095-4.0430.1865655899671490.1433401656472717X-RAY DIFFRACTION98.6574870912
4.043-39.50.1752250156651270.14320681662750X-RAY DIFFRACTION97.0320404722

+
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