[English] 日本語
Yorodumi
- PDB-4alw: Benzofuropyrimidinone Inhibitors of Pim-1 -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 4alw
TitleBenzofuropyrimidinone Inhibitors of Pim-1
ComponentsPIM-1 KINASE
KeywordsTRANSFERASE / PROTO-ONCOGENE SERINE/THREONINE-PROTEIN KINASE PIM-1
Function / homology
Function and homology information


positive regulation of cardioblast proliferation / regulation of hematopoietic stem cell proliferation / vitamin D receptor signaling pathway / cellular detoxification / STAT5 activation downstream of FLT3 ITD mutants / transcription factor binding / ribosomal small subunit binding / positive regulation of cyclin-dependent protein serine/threonine kinase activity / positive regulation of cardiac muscle cell proliferation / negative regulation of innate immune response ...positive regulation of cardioblast proliferation / regulation of hematopoietic stem cell proliferation / vitamin D receptor signaling pathway / cellular detoxification / STAT5 activation downstream of FLT3 ITD mutants / transcription factor binding / ribosomal small subunit binding / positive regulation of cyclin-dependent protein serine/threonine kinase activity / positive regulation of cardiac muscle cell proliferation / negative regulation of innate immune response / positive regulation of brown fat cell differentiation / Signaling by FLT3 fusion proteins / positive regulation of TORC1 signaling / 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 / non-specific serine/threonine protein kinase / protein stabilization / protein phosphorylation / protein serine kinase activity / protein serine/threonine kinase activity / negative regulation of apoptotic process / nucleolus / 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 / : / 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. / Protein kinase domain / Serine/Threonine protein kinases, catalytic domain ...Serine/threonine-protein kinase pim-1/2/3 / : / 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. / 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 / 2-Layer Sandwich / Orthogonal Bundle / Mainly Alpha / Alpha Beta
Similarity search - Domain/homology
Chem-HY7 / IMIDAZOLE / Serine/threonine-protein kinase pim-1
Similarity search - Component
Biological speciesHOMO SAPIENS (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.92 Å
AuthorsStout, T.J. / Adams, L.
CitationJournal: Bioorg.Med.Chem.Lett. / Year: 2012
Title: The Design, Synthesis, and Biological Evaluation of Pim Kinase Inhibitors.
Authors: Tsuhako, A.L. / Brown, D.S. / Koltun, E.S. / Aay, N. / Arcalas, A. / Chan, V. / Du, H. / Engst, S. / Franzini, M. / Galan, A. / Huang, P. / Johnston, S. / Kane, B. / Kim, M.H. / Laird, A.D. ...Authors: Tsuhako, A.L. / Brown, D.S. / Koltun, E.S. / Aay, N. / Arcalas, A. / Chan, V. / Du, H. / Engst, S. / Franzini, M. / Galan, A. / Huang, P. / Johnston, S. / Kane, B. / Kim, M.H. / Laird, A.D. / Lin, R. / Mock, L. / Ngan, I. / Pack, M. / Stott, G. / Stout, T.J. / Yu, P. / Zaharia, C. / Zhang, W. / Zhou, P. / Nuss, J.M. / Kearney, P.C. / Xu, W.
History
DepositionMar 5, 2012Deposition site: PDBE / Processing site: PDBE
Revision 1.0Jan 16, 2013Provider: repository / Type: Initial release
Revision 1.1May 1, 2024Group: Data collection / Database references ...Data collection / Database references / Derived calculations / Other / Refinement description
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / database_2 / pdbx_database_status / pdbx_initial_refinement_model / struct_site
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession ..._database_2.pdbx_DOI / _database_2.pdbx_database_accession / _pdbx_database_status.status_code_sf / _struct_site.pdbx_auth_asym_id / _struct_site.pdbx_auth_comp_id / _struct_site.pdbx_auth_seq_id

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: PIM-1 KINASE
hetero molecules


Theoretical massNumber of molelcules
Total (without water)38,0734
Polymers37,5581
Non-polymers5153
Water6,071337
1


  • Idetical with deposited unit
  • defined by author&software
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
Unit cell
Length a, b, c (Å)97.449, 97.449, 81.003
Angle α, β, γ (deg.)90.00, 90.00, 120.00
Int Tables number170
Space group name H-MP65

-
Components

#1: Protein PIM-1 KINASE


Mass: 37557.652 Da / Num. of mol.: 1 / Fragment: PROTEIN KINASE DOMAIN, RESIDUES 406-717
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) HOMO SAPIENS (human) / Production host: ESCHERICHIA COLI (E. coli) / Strain (production host): BL21 / References: UniProt: P11309, EC: 2.7.1.37
#2: Chemical ChemComp-IMD / IMIDAZOLE


Mass: 69.085 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C3H5N2
#3: Chemical ChemComp-HY7 / 8-BROMANYL-2-[(4-METHYLPIPERAZIN-1-YL)METHYL]-3H-[1]BENZOFURO[3,2-D]PYRIMIDIN-4-ONE


Mass: 377.236 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C16H17BrN4O2
#4: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 337 / 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: 2.9 Å3/Da / Density % sol: 64 % / Description: NONE
Crystal growpH: 7.2 / Details: pH 7.2

-
Data collection

DiffractionMean temperature: 155 K
Diffraction sourceSource: SYNCHROTRON / Site: SSRL / Beamline: BL11-1 / Wavelength: 0.97945
DetectorType: MARMOSAIC 325 mm CCD / Detector: CCD / Date: Jan 4, 2007
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.97945 Å / Relative weight: 1
ReflectionResolution: 1.92→37.42 Å / Num. obs: 33275 / % possible obs: 97.9 % / Observed criterion σ(I): -3 / Redundancy: 7.4 % / Rmerge(I) obs: 0.07 / Net I/σ(I): 17.33
Reflection shellResolution: 1.92→2.03 Å / Redundancy: 5.92 % / Rmerge(I) obs: 1.28 / Mean I/σ(I) obs: 1.6 / % possible all: 95.2

-
Processing

Software
NameVersionClassification
REFMAC5.2.0019refinement
XDSdata reduction
XSCALEdata scaling
PHASERphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: IN-HOUSE PIM1 STRUCTURE

Resolution: 1.92→37.42 Å / Cor.coef. Fo:Fc: 0.975 / Cor.coef. Fo:Fc free: 0.956 / SU B: 3.009 / SU ML: 0.086 / Cross valid method: THROUGHOUT / ESU R: 0.109 / ESU R Free: 0.118 / Stereochemistry target values: MAXIMUM LIKELIHOOD / Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS.
RfactorNum. reflection% reflectionSelection details
Rfree0.20731 1670 5.1 %RANDOM
Rwork0.15516 ---
obs0.15781 31220 98.32 %-
Solvent computationIon probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å / Solvent model: BABINET MODEL WITH MASK
Displacement parametersBiso mean: 37.685 Å2
Baniso -1Baniso -2Baniso -3
1-0 Å20 Å20 Å2
2--0 Å20 Å2
3---0 Å2
Refinement stepCycle: LAST / Resolution: 1.92→37.42 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms2223 0 33 337 2593
Refine LS restraints
Refine-IDTypeDev idealDev ideal targetNumber
X-RAY DIFFRACTIONr_bond_refined_d0.0310.0212363
X-RAY DIFFRACTIONr_bond_other_d
X-RAY DIFFRACTIONr_angle_refined_deg2.2381.9623211
X-RAY DIFFRACTIONr_angle_other_deg
X-RAY DIFFRACTIONr_dihedral_angle_1_deg6.7715280
X-RAY DIFFRACTIONr_dihedral_angle_2_deg33.58523.065124
X-RAY DIFFRACTIONr_dihedral_angle_3_deg13.79515395
X-RAY DIFFRACTIONr_dihedral_angle_4_deg17.3161523
X-RAY DIFFRACTIONr_chiral_restr0.1910.2339
X-RAY DIFFRACTIONr_gen_planes_refined0.0120.021841
X-RAY DIFFRACTIONr_gen_planes_other
X-RAY DIFFRACTIONr_nbd_refined0.2360.21238
X-RAY DIFFRACTIONr_nbd_other
X-RAY DIFFRACTIONr_nbtor_refined0.320.21614
X-RAY DIFFRACTIONr_nbtor_other
X-RAY DIFFRACTIONr_xyhbond_nbd_refined0.2310.2298
X-RAY DIFFRACTIONr_xyhbond_nbd_other
X-RAY DIFFRACTIONr_metal_ion_refined
X-RAY DIFFRACTIONr_metal_ion_other
X-RAY DIFFRACTIONr_symmetry_vdw_refined0.2130.243
X-RAY DIFFRACTIONr_symmetry_vdw_other
X-RAY DIFFRACTIONr_symmetry_hbond_refined0.2780.220
X-RAY DIFFRACTIONr_symmetry_hbond_other
X-RAY DIFFRACTIONr_symmetry_metal_ion_refined
X-RAY DIFFRACTIONr_symmetry_metal_ion_other
X-RAY DIFFRACTIONr_mcbond_it1.8451.51427
X-RAY DIFFRACTIONr_mcbond_other
X-RAY DIFFRACTIONr_mcangle_it2.71522231
X-RAY DIFFRACTIONr_mcangle_other
X-RAY DIFFRACTIONr_scbond_it4.34531141
X-RAY DIFFRACTIONr_scbond_other
X-RAY DIFFRACTIONr_scangle_it6.0364.5976
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: 1.92→1.97 Å / Total num. of bins used: 20
RfactorNum. reflection% reflection
Rfree0.474 142 -
Rwork0.368 2214 -
obs--96.36 %

+
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