[English] 日本語
Yorodumi
- PDB-8cie: Crystal structure of the human CDKL5 kinase domain with compound ... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 8cie
TitleCrystal structure of the human CDKL5 kinase domain with compound YL-354
ComponentsCyclin-dependent kinase-like 5
KeywordsTRANSFERASE / KINASE
Function / homology
Function and homology information


regulation of cilium assembly / regulation of dendrite development / ciliary tip / positive regulation of dendrite morphogenesis / regulation of postsynapse organization / positive regulation of dendritic spine development / dendritic growth cone / postsynaptic density, intracellular component / positive regulation of axon extension / cyclin-dependent kinase ...regulation of cilium assembly / regulation of dendrite development / ciliary tip / positive regulation of dendrite morphogenesis / regulation of postsynapse organization / positive regulation of dendritic spine development / dendritic growth cone / postsynaptic density, intracellular component / positive regulation of axon extension / cyclin-dependent kinase / cyclin-dependent protein serine/threonine kinase activity / dendrite cytoplasm / ciliary basal body / positive regulation of GTPase activity / neuron migration / modulation of chemical synaptic transmission / small GTPase binding / kinase activity / protein autophosphorylation / protein kinase activity / protein phosphorylation / protein serine kinase activity / protein serine/threonine kinase activity / centrosome / glutamatergic synapse / perinuclear region of cytoplasm / nucleoplasm / ATP binding / nucleus
Similarity search - Function
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-US0 / Cyclin-dependent kinase-like 5
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.2 Å
AuthorsRichardson, W. / Chen, X. / Newman, J.A. / Bakshi, S. / Lakshminarayana, B. / Brooke, L. / Bullock, A.N.
Funding support Switzerland, 1items
OrganizationGrant numberCountry
Innovative Medicines Initiative875510 Switzerland
CitationJournal: Acs Chem Neurosci / Year: 2023
Title: Discovery of a Potent and Selective CDKL5/GSK3 Chemical Probe That Is Neuroprotective.
Authors: Ong, H.W. / Liang, Y. / Richardson, W. / Lowry, E.R. / Wells, C.I. / Chen, X. / Silvestre, M. / Dempster, K. / Silvaroli, J.A. / Smith, J.L. / Wichterle, H. / Pabla, N.S. / Ultanir, S.K. / ...Authors: Ong, H.W. / Liang, Y. / Richardson, W. / Lowry, E.R. / Wells, C.I. / Chen, X. / Silvestre, M. / Dempster, K. / Silvaroli, J.A. / Smith, J.L. / Wichterle, H. / Pabla, N.S. / Ultanir, S.K. / Bullock, A.N. / Drewry, D.H. / Axtman, A.D.
History
DepositionFeb 9, 2023Deposition site: PDBE / Processing site: PDBE
Revision 1.0Jun 14, 2023Provider: repository / Type: Initial release
Revision 1.1Mar 27, 2024Group: Data collection / Database references / Category: chem_comp_atom / chem_comp_bond / citation / Item: _citation.pdbx_database_id_PubMed / _citation.title

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Cyclin-dependent kinase-like 5
hetero molecules


Theoretical massNumber of molelcules
Total (without water)35,6773
Polymers35,2321
Non-polymers4452
Water66737
1


  • Idetical with deposited unit
  • defined by author
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area220 Å2
ΔGint-16 kcal/mol
Surface area13060 Å2
Unit cell
Length a, b, c (Å)88.660, 88.660, 131.513
Angle α, β, γ (deg.)90.000, 90.000, 120.000
Int Tables number182
Space group name H-MP6322
Space group name HallP6c2c
Symmetry operation#1: x,y,z
#2: x-y,x,z+1/2
#3: y,-x+y,z+1/2
#4: -y,x-y,z
#5: -x+y,-x,z
#6: x-y,-y,-z
#7: -x,-x+y,-z
#8: -x,-y,z+1/2
#9: y,x,-z
#10: -y,-x,-z+1/2
#11: -x+y,y,-z+1/2
#12: x,x-y,-z+1/2

-
Components

#1: Protein Cyclin-dependent kinase-like 5 / Serine/threonine-protein kinase 9


Mass: 35231.711 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: CDKL5, STK9 / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: O76039, cyclin-dependent kinase
#2: Chemical ChemComp-US0 / 4-[[3,5-bis(fluoranyl)phenyl]carbonylamino]-~{N}-piperidin-4-yl-1~{H}-pyrazole-3-carboxamide


Mass: 349.335 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C16H17F2N5O2 / Feature type: SUBJECT OF INVESTIGATION
#3: Chemical ChemComp-SO4 / SULFATE ION


Mass: 96.063 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: SO4
#4: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 37 / 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: 2.12 Å3/Da / Density % sol: 41.91 %
Crystal growTemperature: 293 K / Method: vapor diffusion
Details: 0.1 M tri-sodium citrate, 1.1 M lithium sulfate, 0.4 M ammonium sulfate

-
Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: Diamond / Beamline: I04 / Wavelength: 0.9763 Å
DetectorType: DECTRIS EIGER X 16M / Detector: PIXEL / Date: Nov 19, 2022
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.9763 Å / Relative weight: 1
ReflectionResolution: 2.2→44.33 Å / Num. obs: 16108 / % possible obs: 99.9 % / Redundancy: 39 % / Biso Wilson estimate: 38.31 Å2 / CC1/2: 1 / Net I/σ(I): 15.5
Reflection shellResolution: 2.2→2.24 Å / Num. unique obs: 759 / CC1/2: 0.9

-
Processing

Software
NameVersionClassification
PHENIX1.13_2998refinement
xia2data reduction
DIALSdata scaling
PHENIXphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT / Resolution: 2.2→44.33 Å / SU ML: 0.3558 / Cross valid method: NONE / σ(F): 1.39 / Phase error: 35.3313 / Stereochemistry target values: GeoStd + Monomer Library
RfactorNum. reflection% reflection
Rfree0.3098 786 4.89 %
Rwork0.2876 15285 -
obs0.2887 16071 99.7 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL
Displacement parametersBiso mean: 58.18 Å2
Refinement stepCycle: LAST / Resolution: 2.2→44.33 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms2193 0 30 37 2260
Refine LS restraints
Refine-IDTypeDev idealNumber
X-RAY DIFFRACTIONf_bond_d0.00542270
X-RAY DIFFRACTIONf_angle_d0.90393080
X-RAY DIFFRACTIONf_chiral_restr0.0572346
X-RAY DIFFRACTIONf_plane_restr0.0065395
X-RAY DIFFRACTIONf_dihedral_angle_d6.20181377
LS refinement shell
Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkRefine-ID% reflection obs (%)
2.2-2.340.37881220.36462473X-RAY DIFFRACTION99.16
2.34-2.520.33741530.34962450X-RAY DIFFRACTION99.73
2.52-2.770.32021330.33522505X-RAY DIFFRACTION99.77
2.77-3.170.35411180.32672539X-RAY DIFFRACTION99.89
3.17-40.32341390.26892557X-RAY DIFFRACTION100
4-44.330.2581210.25072761X-RAY DIFFRACTION99.65
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)
19.460229103461.02230459653-4.764974739078.867456988640.3823139449847.23032626023-0.731325932099-1.07225073856-0.4769470551550.2233868267540.134909537839-0.5392337283661.079717606610.7483496348360.595307224290.503595519810.02177938576260.1671522332410.4522351406850.04921266668870.34844840708226.758208025321.14138119618.66823548659
2-0.0292937714353-0.747922346226-0.9716935818072.489476347432.822345782874.52317176975-0.9298535129280.0246136073959-0.712750761024-0.692781494004-0.1847186133230.5059511360161.39557257106-0.03116060907970.8450365758681.245754418490.09295937287620.3549804726660.4618611774570.0003842896401840.77434780318225.67509968239.55776717096-1.96602125574
32.04923968413-2.371882032163.014540059055.30790770021-2.643204317954.87832164486-0.532495071684-0.354162974862-0.6094876373610.0302299000809-0.102942248319-0.2689362813581.688663370481.479712098430.6041296317850.7106505292960.2189943344240.1820106970590.5380018544430.07399370630080.48527664270832.611203721716.3482177396-0.66524600595
44.989363041310.602467762644-1.332940378522.48738746755-2.458951394627.23624447515-0.0877204795109-0.4036608783710.23161976043-0.0742545702955-0.0600531946857-0.3069065003320.02271189418580.8492460306910.1935993477550.296907947489-0.0731007760870.04663956535640.256702439178-0.001478486645280.23820209461928.136087592627.9841471674-13.6656167641
55.34275746007-1.71564530652-2.527226325772.742270276640.2991627463834.99813347139-0.69014671556-0.537861069892-1.06451498574-0.0773093688029-0.08549698114750.3949658103671.720183961810.1220916627780.5041630290170.911465508022-0.04211659558730.249194582430.2538458502830.0503290316060.46947998356823.002303997917.2860795164-10.228769552
62.08020294383-0.806537351409-0.2231372464214.565393134390.7574323713417.6655955841-0.3536812971790.458294579779-0.313625378551-0.2580522962980.1741806342790.2615718447270.698438018081-1.8762887540.1917270947440.609653297072-0.3307803652930.08423501012330.538409988249-0.1513625846410.39359184729113.187454924523.9191790747-20.4310016493
72.687310570920.3253304337670.9410449224321.858665837580.06405214387060.2709601097620.05928274304880.649117586116-0.197028208957-0.5365903587140.3473791422850.668984842140.877278866395-1.88051061482-0.1565449194940.934939081376-0.749533899904-0.07776849797771.20558945214-0.07009191414170.5419201745215.4393058703422.8165896181-28.5992702155
84.239751639590.6450747726561.000882940935.56556470547-0.09280972736543.31345880783-0.3641193225060.430310870438-0.300512728915-0.4839323657390.239346940935-0.3525764967470.4314748748920.06392592498610.1273229923650.514497185971-0.115221272350.1501709195580.276461718758-0.03626094552460.3824100942128.085633944626.9978398299-27.74946786
Refinement TLS group
IDRefine-IDRefine TLS-IDSelection details
1X-RAY DIFFRACTION1chain 'A' and (resid 14 through 38 )
2X-RAY DIFFRACTION2chain 'A' and (resid 39 through 67 )
3X-RAY DIFFRACTION3chain 'A' and (resid 68 through 91 )
4X-RAY DIFFRACTION4chain 'A' and (resid 92 through 130 )
5X-RAY DIFFRACTION5chain 'A' and (resid 131 through 172 )
6X-RAY DIFFRACTION6chain 'A' and (resid 173 through 228 )
7X-RAY DIFFRACTION7chain 'A' and (resid 229 through 262 )
8X-RAY DIFFRACTION8chain 'A' and (resid 263 through 304 )

+
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://pdbjlvh1.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