[English] 日本語
Yorodumi
- PDB-7qfm: Pim1 in complex with (E)-4-((2-oxoindolin-3-ylidene)methyl)benzoi... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 7qfm
TitlePim1 in complex with (E)-4-((2-oxoindolin-3-ylidene)methyl)benzoic acid and Pimtide
Components
  • Pimtide
  • Serine/threonine-protein kinase pim-1
KeywordsTRANSFERASE / SERINE KINASE / KINASE / COMPLEX / PIM1 / PIM / PIM-1 / INHIBITOR / TUMORIGENISIS / CANCER / PIMTIDE / PROTO ONCOGEN / ATP / PHOSPHORYLATION / APOPTOSIS / CELL CYCLE
Function / homology
Function and homology information


positive regulation of cardioblast proliferation / cellular detoxification / regulation of hematopoietic stem cell proliferation / vitamin D receptor signaling pathway / STAT5 activation downstream of FLT3 ITD mutants / ribosomal small subunit binding / transcription factor binding / positive regulation of cyclin-dependent protein serine/threonine kinase activity / positive regulation of cardiac muscle cell proliferation / positive regulation of TORC1 signaling ...positive regulation of cardioblast proliferation / cellular detoxification / regulation of hematopoietic stem cell proliferation / vitamin D receptor signaling pathway / STAT5 activation downstream of FLT3 ITD mutants / ribosomal small subunit binding / transcription factor binding / positive regulation of cyclin-dependent protein serine/threonine kinase activity / positive regulation of cardiac muscle cell proliferation / positive regulation of TORC1 signaling / Signaling by FLT3 fusion proteins / negative regulation of innate immune response / positive regulation of brown fat cell differentiation / protein serine/threonine kinase activator activity / regulation of transmembrane transporter activity / positive regulation of protein serine/threonine kinase activity / negative regulation of DNA-binding transcription factor activity / cellular response to type II interferon / manganese ion binding / Interleukin-4 and Interleukin-13 signaling / protein autophosphorylation / protein stabilization / non-specific serine/threonine protein kinase / cell cycle / protein phosphorylation / protein serine kinase activity / protein serine/threonine kinase activity / apoptotic process / nucleolus / negative regulation of apoptotic process / positive regulation of DNA-templated transcription / nucleoplasm / ATP binding / nucleus / plasma membrane / cytosol / cytoplasm
Similarity search - Function
Serine/threonine-protein kinase pim-1/2/3 / 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-AY3 / Serine/threonine-protein kinase pim-1
Similarity search - Component
Biological speciesHomo sapiens (human)
synthetic construct (others)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.95 Å
AuthorsHochban, P.M.M. / Heine, A. / Diederich, W.E.
Funding support Germany, 1items
OrganizationGrant numberCountry
Not funded Germany
CitationJournal: Eur.J.Med.Chem. / Year: 2023
Title: Pose, duplicate, then elaborate: Steps towards increased affinity for inhibitors targeting the specificity surface of the Pim-1 kinase.
Authors: Heyder, L. / Hochban, P.M.M. / Taylor, C. / Chevillard, F. / Siefker, C. / Iking, C. / Borchardt, H. / Aigner, A. / Klebe, G. / Heine, A. / Kolb, P. / Diederich, W.E.
History
DepositionDec 6, 2021Deposition site: PDBE / Processing site: PDBE
Revision 1.0Dec 21, 2022Provider: repository / Type: Initial release
Revision 1.1Feb 1, 2023Group: Database references / Source and taxonomy
Category: citation / citation_author ...citation / citation_author / entity_src_gen / pdbx_entity_src_syn
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 / _entity_src_gen.gene_src_common_name / _pdbx_entity_src_syn.organism_scientific
Revision 1.2Feb 7, 2024Group: Data collection / Refinement description
Category: chem_comp_atom / chem_comp_bond / pdbx_initial_refinement_model

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Serine/threonine-protein kinase pim-1
D: Pimtide
hetero molecules


Theoretical massNumber of molelcules
Total (without water)37,5344
Polymers37,1762
Non-polymers3572
Water2,216123
1


  • Idetical with deposited unit
  • defined by author
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area1380 Å2
ΔGint3 kcal/mol
Surface area12620 Å2
Unit cell
Length a, b, c (Å)96.818, 96.818, 80.147
Angle α, β, γ (deg.)90.000, 90.000, 120.000
Int Tables number170
Space group name H-MP65
Space group name HallP65
Symmetry operation#1: x,y,z
#2: x-y,x,z+5/6
#3: y,-x+y,z+1/6
#4: -y,x-y,z+2/3
#5: -x+y,-x,z+1/3
#6: -x,-y,z+1/2

-
Components

#1: Protein Serine/threonine-protein kinase pim-1


Mass: 35583.398 Da / Num. of mol.: 1 / Mutation: R250G
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: PIM1 / Plasmid: pLIC-SGC / Production host: Escherichia coli BL21(DE3) (bacteria)
References: UniProt: P11309, non-specific serine/threonine protein kinase
#2: Protein/peptide Pimtide


Mass: 1592.850 Da / Num. of mol.: 1 / Source method: obtained synthetically / Source: (synth.) synthetic construct (others)
#3: Chemical ChemComp-GOL / GLYCEROL / GLYCERIN / PROPANE-1,2,3-TRIOL / Glycerol


Mass: 92.094 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C3H8O3
#4: Chemical ChemComp-AY3 / 4-[(~{E})-(2-oxidanylidene-1~{H}-indol-3-ylidene)methyl]benzoic acid


Mass: 265.263 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C16H11NO3 / Feature type: SUBJECT OF INVESTIGATION
#5: Water ChemComp-HOH / water / Water


Mass: 18.015 Da / Num. of mol.: 123 / 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: 3.1 Å3/Da / Density % sol: 59.7 %
Crystal growTemperature: 291.15 K / Method: vapor diffusion, sitting drop / pH: 7
Details: 100 mM bis-tris propane (pH 7.0), 10% ethylene glycol, 0.3% DMSO, 20% PEG3350, 200 mM MgOAc
PH range: 6.8 - 7.2

-
Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: BESSY / Beamline: 14.1 / Wavelength: 0.9184 Å
DetectorType: DECTRIS PILATUS 6M / Detector: PIXEL / Date: Oct 23, 2020 / Details: Sagitally bended Si111-crystal
RadiationMonochromator: Double crystal / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.9184 Å / Relative weight: 1
ReflectionResolution: 1.95→48.409 Å / Num. obs: 31177 / % possible obs: 99.7 % / Redundancy: 20.7 % / Biso Wilson estimate: 34.91 Å2 / CC1/2: 1 / Rsym value: 0.038 / Net I/σ(I): 50
Reflection shellResolution: 1.95→2.07 Å / Redundancy: 21 % / Mean I/σ(I) obs: 7.8 / Num. unique obs: 4980 / CC1/2: 1 / Rsym value: 0.44 / % possible all: 99

-
Processing

Software
NameVersionClassification
PHENIX1.16_3549refinement
MxCuBEdata collection
XDS1.02data reduction
XDS1.02data scaling
Coot0.7.1model building
PHASERphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 5NDT

5ndt


Resolution: 1.95→41.92 Å / SU ML: 0.145 / Cross valid method: FREE R-VALUE / σ(F): 1.38 / Phase error: 17.2189
Stereochemistry target values: GeoStd + Monomer Library + CDL v1.2
RfactorNum. reflection% reflection
Rfree0.1779 1556 4.99 %
Rwork0.1583 29596 -
obs0.1593 31152 99.62 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL
Displacement parametersBiso mean: 43.25 Å2
Refinement stepCycle: LAST / Resolution: 1.95→41.92 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms2196 0 26 123 2345
Refine LS restraints
Refine-IDTypeDev idealNumber
X-RAY DIFFRACTIONf_bond_d0.00672316
X-RAY DIFFRACTIONf_angle_d0.7853147
X-RAY DIFFRACTIONf_chiral_restr0.0539339
X-RAY DIFFRACTIONf_plane_restr0.005428
X-RAY DIFFRACTIONf_dihedral_angle_d21.23911373
LS refinement shell
Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkRefine-ID% reflection obs (%)
1.95-2.010.1871380.16052638X-RAY DIFFRACTION98.37
2.01-2.080.17431400.14612671X-RAY DIFFRACTION99.61
2.08-2.170.17971410.14822681X-RAY DIFFRACTION99.72
2.17-2.260.17851410.1582686X-RAY DIFFRACTION99.93
2.26-2.380.15991410.15182673X-RAY DIFFRACTION99.54
2.38-2.530.20121410.16132701X-RAY DIFFRACTION99.93
2.53-2.730.18841420.17072687X-RAY DIFFRACTION99.96
2.73-30.1811420.16752704X-RAY DIFFRACTION100
3-3.440.18621420.16212698X-RAY DIFFRACTION99.65
3.44-4.330.16721430.15072711X-RAY DIFFRACTION99.93
4.33-41.920.17681450.15952746X-RAY DIFFRACTION99.42
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)
10.8652172382230.04222265832940.210935880170.241390367441-0.09852442304920.492829268112-0.1506172258730.547168299505-0.0500016634972-0.03858694129460.22274528165-0.306653817663-0.1690956945460.4049562251050.000144009431840.380252986699-0.1072112011180.01846517216460.468447006176-0.02984221758260.477885022199-111.907906765201.102242541-8.57846559787
20.82228825180.1977622868330.6551571728690.284197404932-0.1239764123710.8565434959920.130413046262-0.01293837166160.369176734830.1828143025860.0285232788645-0.114119543413-0.4029384669130.2725311934320.00704516938070.354425024653-0.06576304909270.006820524084360.314558976863-0.01459189331380.344287018066-121.039892326203.173365297-3.3136298864
31.687417588150.161437291373-0.4536004574170.7996302024250.1891149970522.40321695575-0.0129520338311-0.0437729931992-0.02074778238680.06682950709970.0540551606524-0.0266419645660.111307453036-0.07529577251090.0001260593003870.241023465946-0.0341414522863-0.02440504934140.160461962501-0.007189023531140.198967813345-134.161464307191.1464773240.750284015915
40.250280592357-0.227199914557-0.3663578780941.61837108507-0.2467510945840.7739862233640.0343281944168-0.342460547965-0.3115395610080.8549014474020.3015266437030.008788118978540.5138807442970.3234757030620.01495366245170.429120657107-0.0386425060188-0.1022348976270.577954072229-0.03346975682620.379593173987-123.65150589192.79218957412.8723187049
Refinement TLS group
IDRefine-IDRefine TLS-IDSelection details
1X-RAY DIFFRACTION1chain 'A' and (resid 33 through 96 )
2X-RAY DIFFRACTION2chain 'A' and (resid 97 through 140 )
3X-RAY DIFFRACTION3chain 'A' and (resid 141 through 305 )
4X-RAY DIFFRACTION4chain 'D' and (resid 2 through 9 )

+
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