[English] 日本語
Yorodumi
- PDB-3zh8: A novel small molecule aPKC inhibitor -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 3zh8
TitleA novel small molecule aPKC inhibitor
ComponentsPROTEIN KINASE C IOTA TYPE
KeywordsTRANSFERASE / AGC KINASES / CELL POLARITY / CELL MIGRATION
Function / homology
Function and homology information


Golgi vesicle budding / PAR polarity complex / Tight junction interactions / establishment of apical/basal cell polarity / protein kinase C / negative regulation of glial cell apoptotic process / diacylglycerol-dependent serine/threonine kinase activity / eye photoreceptor cell development / Schmidt-Lanterman incisure / cellular response to chemical stress ...Golgi vesicle budding / PAR polarity complex / Tight junction interactions / establishment of apical/basal cell polarity / protein kinase C / negative regulation of glial cell apoptotic process / diacylglycerol-dependent serine/threonine kinase activity / eye photoreceptor cell development / Schmidt-Lanterman incisure / cellular response to chemical stress / membrane organization / cell-cell junction organization / establishment or maintenance of epithelial cell apical/basal polarity / positive regulation of endothelial cell apoptotic process / tight junction / protein targeting to membrane / intercellular bridge / positive regulation of Notch signaling pathway / cell leading edge / regulation of postsynaptic membrane neurotransmitter receptor levels / brush border / bicellular tight junction / cytoskeleton organization / positive regulation of glial cell proliferation / vesicle-mediated transport / p75NTR recruits signalling complexes / response to interleukin-1 / secretion / actin filament organization / phospholipid binding / positive regulation of protein localization to plasma membrane / positive regulation of glucose import / Schaffer collateral - CA1 synapse / positive regulation of neuron projection development / Pre-NOTCH Transcription and Translation / cellular response to insulin stimulus / microtubule cytoskeleton / KEAP1-NFE2L2 pathway / cell migration / positive regulation of NF-kappaB transcription factor activity / negative regulation of neuron apoptotic process / endosome / protein kinase activity / intracellular signal transduction / apical plasma membrane / Golgi membrane / protein phosphorylation / protein serine kinase activity / protein serine/threonine kinase activity / glutamatergic synapse / negative regulation of apoptotic process / extracellular exosome / nucleoplasm / ATP binding / metal ion binding / nucleus / plasma membrane / cytosol
Similarity search - Function
Atypical protein kinase C iota type, catalytic domain / Protein kinase C / Protein kinase C, PB1 domain / PB1 domain / PB1 domain / PB1 domain profile. / PB1 domain / Protein kinase, C-terminal / Protein kinase C terminal domain / Diacylglycerol/phorbol-ester binding ...Atypical protein kinase C iota type, catalytic domain / Protein kinase C / Protein kinase C, PB1 domain / PB1 domain / PB1 domain / PB1 domain profile. / PB1 domain / Protein kinase, C-terminal / Protein kinase C terminal domain / Diacylglycerol/phorbol-ester binding / Phorbol esters/diacylglycerol binding domain (C1 domain) / Zinc finger phorbol-ester/DAG-type signature. / Zinc finger phorbol-ester/DAG-type profile. / Protein kinase C conserved region 1 (C1) domains (Cysteine-rich domains) / Protein kinase C-like, phorbol ester/diacylglycerol-binding domain / C1-like domain superfamily / Extension to Ser/Thr-type protein kinases / AGC-kinase, C-terminal / AGC-kinase C-terminal domain profile. / 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-C58 / IODIDE ION / Protein kinase C iota type
Similarity search - Component
Biological speciesHOMO SAPIENS (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.739 Å
AuthorsKjaer, S. / Purkiss, A.G. / Kostelecky, B. / Knowles, P.P. / Soriano, E. / Murray-Rust, J. / McDonald, N.Q.
CitationJournal: Biochem.J. / Year: 2013
Title: Adenosine-Binding Motif Mimicry and Cellular Effects of a Thieno[2,3-D]Pyrimidine-Based Chemical Inhibitor of Atypical Protein Kinase C Isozymes.
Authors: Kjaer, S. / Linch, M. / Purkiss, A. / Kostelecky, B. / Knowles, P.P. / Rosse, C. / Riou, P. / Soudy, C. / Kaye, S. / Patel, B. / Soriano, E. / Murray-Rust, J. / Barton, C. / Dillon, C. / ...Authors: Kjaer, S. / Linch, M. / Purkiss, A. / Kostelecky, B. / Knowles, P.P. / Rosse, C. / Riou, P. / Soudy, C. / Kaye, S. / Patel, B. / Soriano, E. / Murray-Rust, J. / Barton, C. / Dillon, C. / Roffey, J. / Parker, P.J. / Mcdonald, N.Q.
History
DepositionDec 20, 2012Deposition site: PDBE / Processing site: PDBE
Revision 1.0Feb 27, 2013Provider: repository / Type: Initial release
Revision 1.1Apr 17, 2013Group: Database references
Revision 1.2Apr 3, 2019Group: Data collection / Derived calculations ...Data collection / Derived calculations / Other / Source and taxonomy
Category: entity_src_gen / pdbx_database_proc ...entity_src_gen / pdbx_database_proc / pdbx_database_status / pdbx_seq_map_depositor_info / struct_conn
Item: _entity_src_gen.pdbx_host_org_cell_line / _pdbx_database_status.recvd_author_approval ..._entity_src_gen.pdbx_host_org_cell_line / _pdbx_database_status.recvd_author_approval / _pdbx_seq_map_depositor_info.one_letter_code / _struct_conn.pdbx_leaving_atom_flag
Revision 1.3Dec 20, 2023Group: 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_conn / 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_conn.pdbx_dist_value / _struct_conn.ptnr1_auth_comp_id / _struct_conn.ptnr1_auth_seq_id / _struct_conn.ptnr1_label_atom_id / _struct_conn.ptnr1_label_comp_id / _struct_conn.ptnr1_label_seq_id / _struct_conn.ptnr2_auth_comp_id / _struct_conn.ptnr2_auth_seq_id / _struct_conn.ptnr2_label_atom_id / _struct_conn.ptnr2_label_comp_id / _struct_conn.ptnr2_label_seq_id / _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: PROTEIN KINASE C IOTA TYPE
B: PROTEIN KINASE C IOTA TYPE
C: PROTEIN KINASE C IOTA TYPE
hetero molecules


Theoretical massNumber of molelcules
Total (without water)124,44931
Polymers120,9523
Non-polymers3,49728
Water1,31573
1
A: PROTEIN KINASE C IOTA TYPE
hetero molecules


Theoretical massNumber of molelcules
Total (without water)41,46210
Polymers40,3171
Non-polymers1,1459
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
2
B: PROTEIN KINASE C IOTA TYPE
hetero molecules


Theoretical massNumber of molelcules
Total (without water)41,52411
Polymers40,3171
Non-polymers1,20710
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
3
C: PROTEIN KINASE C IOTA TYPE
hetero molecules


Theoretical massNumber of molelcules
Total (without water)41,46210
Polymers40,3171
Non-polymers1,1459
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
Unit cell
Length a, b, c (Å)113.580, 113.580, 82.410
Angle α, β, γ (deg.)90.00, 90.00, 120.00
Int Tables number144
Space group name H-MP31

-
Components

-
Protein , 1 types, 3 molecules ABC

#1: Protein PROTEIN KINASE C IOTA TYPE / PKC IOTA / ATYPICAL PROTEIN KINASE C-LAMBDA/IOTA / PRKC-LAMBDA/IOTA / APKC-LAMBDA/IOTA / NPKC-IOTA


Mass: 40317.320 Da / Num. of mol.: 3 / Fragment: KINASE DOMAIN, RESIDUES 248-596 / Mutation: YES
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) HOMO SAPIENS (human) / Plasmid: PBACPAK-HIS3 / Cell line (production host): High Five / Production host: SPODOPTERA FRUGIPERDA (fall armyworm) / References: UniProt: P41743, protein kinase C

-
Non-polymers , 5 types, 101 molecules

#2: Chemical
ChemComp-IOD / IODIDE ION / Iodide


Mass: 126.904 Da / Num. of mol.: 12 / Source method: obtained synthetically / Formula: I
#3: Chemical ChemComp-CL / CHLORIDE ION / Chloride


Mass: 35.453 Da / Num. of mol.: 3 / Source method: obtained synthetically / Formula: Cl
#4: Chemical ChemComp-C58 / (2S)-3-phenyl-N~1~-[2-(pyridin-4-yl)-5,6,7,8-tetrahydro[1]benzothieno[2,3-d]pyrimidin-4-yl]propane-1,2-diamine


Mass: 415.554 Da / Num. of mol.: 3 / Source method: obtained synthetically / Formula: C24H25N5S
#5: Chemical
ChemComp-EDO / 1,2-ETHANEDIOL / ETHYLENE GLYCOL / Ethylene glycol


Mass: 62.068 Da / Num. of mol.: 10 / Source method: obtained synthetically / Formula: C2H6O2
#6: Water ChemComp-HOH / water / Water


Mass: 18.015 Da / Num. of mol.: 73 / Source method: isolated from a natural source / Formula: H2O

-
Details

Nonpolymer details1,2-ETHANEDIOL (EDO): CRYOPROTECTANT (S)-N*1*-(2-PYRIDIN-4-YL-5,6,7,8-TETRAHYDRO-BENZO[4, 5] ...1,2-ETHANEDIOL (EDO): CRYOPROTECTANT (S)-N*1*-(2-PYRIDIN-4-YL-5,6,7,8-TETRAHYDRO-BENZO[4, 5]THIENO[2,3-D]PYRIMIDIN-4-YL)-BUTANE-1,2-DIAMINE (C58): CRT0066854

-
Experimental details

-
Experiment

ExperimentMethod: X-RAY DIFFRACTION / Number of used crystals: 1

-
Sample preparation

CrystalDensity Matthews: 2.56 Å3/Da / Density % sol: 51.9 % / Description: NONE
Crystal growDetails: 0.2M AMMONIUM IODIDE AND 20%(W/V) PEG3350.

-
Data collection

DiffractionMean temperature: 199 K
Diffraction sourceSource: SYNCHROTRON / Site: Diamond / Beamline: I03 / Wavelength: 0.92
DetectorType: ADSC CCD / Detector: CCD / Date: Jan 27, 2008 / Details: MIRRORS
RadiationMonochromator: SI CRYSTAL / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.92 Å / Relative weight: 1
ReflectionResolution: 2.74→49.21 Å / Num. obs: 31307 / % possible obs: 95.6 % / Observed criterion σ(I): 1.2 / Redundancy: 1.94 % / Biso Wilson estimate: 50.84 Å2 / Rmerge(I) obs: 0.1 / Net I/σ(I): 7.4
Reflection shellResolution: 2.74→2.89 Å / Redundancy: 1.88 % / Rmerge(I) obs: 0.62 / Mean I/σ(I) obs: 1.24 / % possible all: 95.1

-
Processing

Software
NameVersionClassification
PHENIX(PHENIX.REFINE: 1.8.1_1168)refinement
iMOSFLMdata reduction
SCALAdata scaling
PHASERphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: PDB ENTRY 1ZRZ

1zrz


Resolution: 2.739→42.233 Å / SU ML: 0.41 / σ(F): 2.03 / Phase error: 26.81 / Stereochemistry target values: ML
Details: RESIDUES 448-455 ARE NOT VISIBLE IN ELECTRON DENSITY. RESIDUES 538-552 ARE NOT VISIBLE IN ELECTRON DENSITY, HOWEVER THERE IS SOME UNMODELLED DENSITY AROUND THE NCS TWO FOLD NEAR THIS REGION ...Details: RESIDUES 448-455 ARE NOT VISIBLE IN ELECTRON DENSITY. RESIDUES 538-552 ARE NOT VISIBLE IN ELECTRON DENSITY, HOWEVER THERE IS SOME UNMODELLED DENSITY AROUND THE NCS TWO FOLD NEAR THIS REGION ELECTRON DENSITY PRESENT AT THE NCS 2-FOLD BETWEEN CHAINS A AND B. THIS PROBABLY REPRESENTS PART OF THE MISSING LOOP BETWEEN RESIDUES 538 AND 553 BUT HAS NOT BEEN MODELLED.
RfactorNum. reflection% reflection
Rfree0.2568 1576 5 %
Rwork0.2103 --
obs0.2126 31270 99.97 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL
Refinement stepCycle: LAST / Resolution: 2.739→42.233 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms7496 0 145 73 7714
Refine LS restraints
Refine-IDTypeDev idealNumber
X-RAY DIFFRACTIONf_bond_d0.0037807
X-RAY DIFFRACTIONf_angle_d0.68710571
X-RAY DIFFRACTIONf_dihedral_angle_d11.6652876
X-RAY DIFFRACTIONf_chiral_restr0.0451138
X-RAY DIFFRACTIONf_plane_restr0.0031439
LS refinement shell
Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkRefine-ID% reflection obs (%)
2.7392-2.82760.33991580.29742685X-RAY DIFFRACTION100
2.8276-2.92870.32131590.27622701X-RAY DIFFRACTION100
2.9287-3.04590.28351270.25622703X-RAY DIFFRACTION100
3.0459-3.18450.34541470.25592703X-RAY DIFFRACTION100
3.1845-3.35230.34161360.23692702X-RAY DIFFRACTION100
3.3523-3.56220.26381640.22292690X-RAY DIFFRACTION100
3.5622-3.83710.25541490.19292678X-RAY DIFFRACTION100
3.8371-4.22290.25721340.18682702X-RAY DIFFRACTION100
4.2229-4.83320.2131250.16622733X-RAY DIFFRACTION100
4.8332-6.08650.2181520.19282689X-RAY DIFFRACTION100
6.0865-42.23760.2041250.20812708X-RAY DIFFRACTION100
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)
12.44820.2406-1.20291.0332-0.46491.3348-0.03850.10030.418-0.13360.1674-0.0226-1.02020.8101-0.12840.7386-0.38080.13130.6382-0.03060.444821.833522.06924.1228
24.48461.1096-2.82091.5631-0.25494.17550.31940.28050.18060.2035-0.15930.2083-0.8391-0.279-0.09080.47870.04640.01630.30660.05750.3226-1.469317.698311.9994
31.44131.1990.63152.3055-0.80031.5952-0.12550.4019-0.0393-0.14440.3937-0.3288-0.84171.1021-0.16450.6988-0.44270.13290.9924-0.00220.517426.602918.5378-3.9337
43.78020.6281-0.15781.8062-0.37911.4236-0.05860.1123-0.02320.06510.2410.35710.273-1.0218-0.17030.3488-0.13440.04630.75420.07580.40526.390125.04446.6425
53.18411.1447-1.59622.3076-1.57464.75920.04260.09760.23990.24410.07020.084-0.5239-0.5781-0.01940.26990.0702-0.00940.3057-0.02080.303242.232343.02239.1052
64.9432-3.05223.64852.1108-1.85143.3219-0.0115-0.6497-0.9442-0.23620.41270.8270.6094-1.2078-0.45760.4245-0.22060.05060.83410.11040.544927.776118.286455.6103
71.4804-0.61271.59422.70131.02052.86690.1055-0.17390.3267-0.2937-0.11-0.6888-0.1080.73290.03490.4781-0.0940.16760.805-0.06960.953230.602968.4831-3.438
82.35891.35630.22442.3209-0.30823.50590.0377-0.02810.0238-0.2601-0.00920.29180.25170.111-0.03750.45880.10080.00840.3961-0.02560.551213.363353.0545-11.1629
96.04710.5548-1.76245.29862.00894.01880.3746-0.47080.47930.23130.45-0.9109-0.47240.8913-0.84660.6147-0.34880.12021.0307-0.21250.771630.910875.7445.8977
Refinement TLS group
IDRefine-IDRefine TLS-IDSelection details
1X-RAY DIFFRACTION1CHAIN A AND (RESID 239:329 )
2X-RAY DIFFRACTION2CHAIN A AND (RESID 330:525)
3X-RAY DIFFRACTION3CHAIN A AND (RESID 553:581 )
4X-RAY DIFFRACTION4CHAIN B AND (RESID 239:329 )
5X-RAY DIFFRACTION5CHAIN B AND (RESID 330:525 )
6X-RAY DIFFRACTION6CHAIN B AND (RESID 553:581 )
7X-RAY DIFFRACTION7CHAIN C AND (RESID 239:329 )
8X-RAY DIFFRACTION8CHAIN C AND (RESID 330:533 )
9X-RAY DIFFRACTION9CHAIN C AND (RESID 553:581 )

+
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