[English] 日本語
Yorodumi
- PDB-7xsv: Crystal Structures of PIM1 in Complex with Macrocyclic Compound H3 -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 7xsv
TitleCrystal Structures of PIM1 in Complex with Macrocyclic Compound H3
ComponentsSerine/threonine-protein kinase pim-1
KeywordsTRANSFERASE / Pim-1 kinase / Compound H3 / TRANSFERASE-INHIBITOR complex
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 / positive regulation of cyclin-dependent protein serine/threonine kinase activity / ribosomal small subunit binding / positive regulation of cardiac muscle cell proliferation / Signaling by FLT3 fusion proteins ...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 / positive regulation of cyclin-dependent protein serine/threonine kinase activity / ribosomal small subunit binding / positive regulation of cardiac muscle cell proliferation / Signaling by FLT3 fusion proteins / positive regulation of TORC1 signaling / 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 / protein phosphorylation / protein serine kinase activity / protein serine/threonine kinase activity / nucleolus / negative regulation of apoptotic process / 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-I4M / Serine/threonine-protein kinase pim-1
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / molecular replacement / Resolution: 2.66 Å
AuthorsShen, C. / Xie, Y. / Ren, X. / Zhou, Y. / Niu, H.
Funding support China, 1items
OrganizationGrant numberCountry
Beijing Municipal Science & Technology CommissionZ201100005320012 China
CitationJournal: Bioorg.Med.Chem.Lett. / Year: 2022
Title: Design, synthesis, and bioactivity evaluation of macrocyclic benzo[b]pyrido[4,3-e][1,4]oxazine derivatives as novel Pim-1 kinase inhibitors.
Authors: Xu, J. / Shen, C. / Xie, Y. / Qiu, B. / Ren, X. / Zhou, Y. / Li, G. / Zheng, G. / Huang, N.
History
DepositionMay 15, 2022Deposition site: PDBJ / Processing site: PDBJ
Revision 1.0Jul 13, 2022Provider: repository / Type: Initial release
Revision 1.1Nov 29, 2023Group: 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
hetero molecules


Theoretical massNumber of molelcules
Total (without water)33,6482
Polymers33,2931
Non-polymers3551
Water28816
1


  • Idetical with deposited unit
  • defined by author
  • Evidence: gel filtration
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area0 Å2
ΔGint0 kcal/mol
Surface area12820 Å2
Unit cell
Length a, b, c (Å)97.111, 97.111, 78.955
Angle α, β, γ (deg.)90.000, 90.000, 120.000
Int Tables number170
Space group name H-MP65

-
Components

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


Mass: 33292.719 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: PIM1 / Plasmid: pET28 / Production host: Escherichia coli (E. coli) / Strain (production host): BL21(DE3
References: UniProt: P11309, non-specific serine/threonine protein kinase
#2: Chemical ChemComp-I4M / 8-Methyl-2,5,20-trioxa-8,13,17-triazatetracyclo[11.10.2.014,19.021,25]pentacosa-1(24),14(19),15,17,21(25),22-hexaene


Mass: 355.431 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C20H25N3O3 / Feature type: SUBJECT OF INVESTIGATION
#3: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 16 / 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: 3.24 Å3/Da / Density % sol: 61.99 % / Mosaicity: 0.34 °
Crystal growTemperature: 291 K / Method: vapor diffusion, hanging drop / pH: 8 / Details: 0.4M POTASSIUM SODIUM TARTRATE

-
Data collection

DiffractionMean temperature: 291 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: SSRF / Beamline: BL10U2 / Wavelength: 0.9792 Å
DetectorType: DECTRIS EIGER X 16M / Detector: PIXEL / Date: Jan 24, 2022
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.9792 Å / Relative weight: 1
ReflectionResolution: 2.66→41.36 Å / Num. obs: 11558 / % possible obs: 93.7 % / Redundancy: 19.3 % / Biso Wilson estimate: 62.51 Å2 / CC1/2: 0.999 / Rmerge(I) obs: 0.152 / Rpim(I) all: 0.035 / Rrim(I) all: 0.156 / Net I/σ(I): 16 / Num. measured all: 223541 / Scaling rejects: 36
Reflection shell

Diffraction-ID: 1

Resolution (Å)Redundancy (%)Rmerge(I) obsNum. measured allNum. unique obsCC1/2Rpim(I) allRrim(I) allNet I/σ(I) obs% possible all
2.66-2.7919.91.6263148515800.6810.3721.6692.496.8
8.81-41.3614.80.05652013510.9980.0140.05840.198.9

-
Phasing

PhasingMethod: molecular replacement

-
Processing

Software
NameVersionClassification
PHENIX1.19.2refinement
Aimless0.7.7data scaling
PHASER2.8.3phasing
PDB_EXTRACT3.27data extraction
XDSFeb 5, 2021data reduction
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 6KZI

6kzi


Resolution: 2.66→31.79 Å / SU ML: 0.4 / Cross valid method: THROUGHOUT / σ(F): 1.36 / Phase error: 27.27 / Stereochemistry target values: ML
RfactorNum. reflection% reflection
Rfree0.2332 1138 9.87 %
Rwork0.1927 10391 -
obs0.1969 11529 94.04 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL
Displacement parametersBiso max: 142.54 Å2 / Biso mean: 69.231 Å2 / Biso min: 30 Å2
Refinement stepCycle: final / Resolution: 2.66→31.79 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms2227 0 26 16 2269
Biso mean--57.33 59.99 -
Num. residues----274
LS refinement shell

Refine-ID: X-RAY DIFFRACTION / Rfactor Rfree error: 0 / Total num. of bins used: 8

Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkNum. reflection all% reflection obs (%)
2.66-2.780.32421540.283713741528100
2.78-2.930.35081470.270513641511100
2.93-3.110.32671500.245813751525100
3.11-3.330.28461420.22691248139099
3.38-3.690.25671110.20921004111582
3.69-4.220.23641340.17171229136389
4.22-5.310.16981510.155313801531100
5.31-31.790.20171490.176514171566100
Refinement TLS params.Method: refined / Origin x: 66.3593 Å / Origin y: 27.0983 Å / Origin z: 0.8465 Å
111213212223313233
T0.3705 Å2-0.031 Å2-0.0579 Å2-0.3544 Å2-0.0308 Å2--0.3765 Å2
L2.687 °21.5997 °2-0.923 °2-4.131 °2-1.3502 °2--2.8114 °2
S0.1618 Å °-0.0298 Å °0.1592 Å °0.1095 Å °-0.0349 Å °0.5086 Å °-0 Å °0.1903 Å °-0.1015 Å °
Refinement TLS groupSelection details: all

+
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://pdbjlc1.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