[English] 日本語
Yorodumi
- PDB-8d6e: Crystal Structure of Human Myt1 Kinase domain Bounded with RP-6306 -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 8d6e
TitleCrystal Structure of Human Myt1 Kinase domain Bounded with RP-6306
ComponentsMembrane-associated tyrosine- and threonine-specific cdc2-inhibitory kinase
KeywordsSIGNALING PROTEIN / Transferase/Inhibitor / Kinase Inhibitor complex / Transferase-Inhibitor complex
Function / homology
Function and homology information


negative regulation of G2/MI transition of meiotic cell cycle / G2/M DNA replication checkpoint / negative regulation of G2/M transition of mitotic cell cycle / Polo-like kinase mediated events / regulation of mitotic nuclear division / regulation of cyclin-dependent protein serine/threonine kinase activity / Cyclin A/B1/B2 associated events during G2/M transition / meiotic cell cycle / G2/M transition of mitotic cell cycle / kinase activity ...negative regulation of G2/MI transition of meiotic cell cycle / G2/M DNA replication checkpoint / negative regulation of G2/M transition of mitotic cell cycle / Polo-like kinase mediated events / regulation of mitotic nuclear division / regulation of cyclin-dependent protein serine/threonine kinase activity / Cyclin A/B1/B2 associated events during G2/M transition / meiotic cell cycle / G2/M transition of mitotic cell cycle / kinase activity / mitotic cell cycle / protein tyrosine kinase activity / non-specific serine/threonine protein kinase / protein kinase activity / phosphorylation / Golgi membrane / protein serine kinase activity / protein serine/threonine kinase activity / endoplasmic reticulum membrane / nucleolus / Golgi apparatus / endoplasmic reticulum / nucleoplasm / ATP binding / membrane / nucleus / metal ion binding / cytoplasm / cytosol
Similarity search - Function
Tyrosine/threonine-protein kinase, Cdc2 inhibitor / 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-QGI / Membrane-associated tyrosine- and threonine-specific cdc2-inhibitory kinase
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.15 Å
AuthorsPau, V.P.T. / Mao, D.Y.L. / Mader, P. / Orlicky, S. / Sicheri, F.
Funding support Canada, 2items
OrganizationGrant numberCountry
Ontario Research FundRE08-065 Canada
Other private
CitationJournal: J.Med.Chem. / Year: 2022
Title: Discovery of an Orally Bioavailable and Selective PKMYT1 Inhibitor, RP-6306.
Authors: Szychowski, J. / Papp, R. / Dietrich, E. / Liu, B. / Vallee, F. / Leclaire, M.E. / Fourtounis, J. / Martino, G. / Perryman, A.L. / Pau, V. / Yin, S.Y. / Mader, P. / Roulston, A. / Truchon, J. ...Authors: Szychowski, J. / Papp, R. / Dietrich, E. / Liu, B. / Vallee, F. / Leclaire, M.E. / Fourtounis, J. / Martino, G. / Perryman, A.L. / Pau, V. / Yin, S.Y. / Mader, P. / Roulston, A. / Truchon, J.F. / Marshall, C.G. / Diallo, M. / Duffy, N.M. / Stocco, R. / Godbout, C. / Bonneau-Fortin, A. / Kryczka, R. / Bhaskaran, V. / Mao, D. / Orlicky, S. / Beaulieu, P. / Turcotte, P. / Kurinov, I. / Sicheri, F. / Mamane, Y. / Gallant, M. / Black, W.C.
History
DepositionJun 6, 2022Deposition site: RCSB / Processing site: RCSB
Revision 1.0Jul 27, 2022Provider: repository / Type: Initial release
Revision 1.1Aug 10, 2022Group: Database references / Category: citation / citation_author
Item: _citation.journal_abbrev / _citation.journal_id_ISSN ..._citation.journal_abbrev / _citation.journal_id_ISSN / _citation.pdbx_database_id_DOI / _citation.pdbx_database_id_PubMed / _citation.title / _citation.year / _citation_author.identifier_ORCID / _citation_author.name
Revision 1.2Aug 24, 2022Group: Database references / Category: citation / citation_author
Item: _citation.journal_volume / _citation.page_first ..._citation.journal_volume / _citation.page_first / _citation.page_last / _citation_author.identifier_ORCID
Revision 1.3Oct 18, 2023Group: Data collection / Refinement description
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / pdbx_initial_refinement_model / struct_ncs_dom_lim
Item: _struct_ncs_dom_lim.beg_auth_comp_id / _struct_ncs_dom_lim.beg_label_asym_id ..._struct_ncs_dom_lim.beg_auth_comp_id / _struct_ncs_dom_lim.beg_label_asym_id / _struct_ncs_dom_lim.beg_label_comp_id / _struct_ncs_dom_lim.beg_label_seq_id / _struct_ncs_dom_lim.end_auth_comp_id / _struct_ncs_dom_lim.end_label_asym_id / _struct_ncs_dom_lim.end_label_comp_id / _struct_ncs_dom_lim.end_label_seq_id

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
B: Membrane-associated tyrosine- and threonine-specific cdc2-inhibitory kinase
A: Membrane-associated tyrosine- and threonine-specific cdc2-inhibitory kinase
hetero molecules


Theoretical massNumber of molelcules
Total (without water)70,85821
Polymers68,9962
Non-polymers1,86219
Water1,69394
1
B: Membrane-associated tyrosine- and threonine-specific cdc2-inhibitory kinase
hetero molecules


Theoretical massNumber of molelcules
Total (without water)35,50511
Polymers34,4981
Non-polymers1,00710
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
2
A: Membrane-associated tyrosine- and threonine-specific cdc2-inhibitory kinase
hetero molecules


Theoretical massNumber of molelcules
Total (without water)35,35310
Polymers34,4981
Non-polymers8559
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
Unit cell
Length a, b, c (Å)51.243, 112.014, 72.978
Angle α, β, γ (deg.)90.000, 109.870, 90.000
Int Tables number4
Space group name H-MP1211
Noncrystallographic symmetry (NCS)NCS domain:
IDEns-IDDetails
11(chain A and (resid 77 through 165 or (resid 166...
21(chain B and ((resid 77 through 78 and (name N...

NCS domain segments:

Ens-ID: 1

Dom-IDComponent-IDBeg auth comp-IDBeg label comp-IDEnd auth comp-IDEnd label comp-IDSelection detailsAuth asym-IDLabel asym-IDAuth seq-IDLabel seq-ID
11LEULEUGLYGLY(chain A and (resid 77 through 165 or (resid 166...AB77 - 16526 - 114
12GLNGLNGLNGLN(chain A and (resid 77 through 165 or (resid 166...AB166115
13LEULEUGLNGLN(chain A and (resid 77 through 165 or (resid 166...AB77 - 36126 - 310
14LEULEUGLNGLN(chain A and (resid 77 through 165 or (resid 166...AB77 - 36126 - 310
15LEULEUGLNGLN(chain A and (resid 77 through 165 or (resid 166...AB77 - 36126 - 310
16LEULEUGLNGLN(chain A and (resid 77 through 165 or (resid 166...AB77 - 36126 - 310
17LEULEUGLNGLN(chain A and (resid 77 through 165 or (resid 166...AB77 - 36126 - 310
21LEULEUGLNGLN(chain B and ((resid 77 through 78 and (name N...BA77 - 7826 - 27
22LEULEUGLNGLN(chain B and ((resid 77 through 78 and (name N...BA77 - 36126 - 310
23LEULEUGLNGLN(chain B and ((resid 77 through 78 and (name N...BA77 - 36126 - 310
24LEULEUGLNGLN(chain B and ((resid 77 through 78 and (name N...BA77 - 36126 - 310
25LEULEUGLNGLN(chain B and ((resid 77 through 78 and (name N...BA77 - 36126 - 310

-
Components

-
Protein , 1 types, 2 molecules BA

#1: Protein Membrane-associated tyrosine- and threonine-specific cdc2-inhibitory kinase / Myt1 kinase


Mass: 34498.133 Da / Num. of mol.: 2 / Fragment: KINASE DOMAIN, UNP RESIDUES 75-362
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: PKMYT1, MYT1 / Plasmid: pNIC28-Bsa4 / Production host: Escherichia coli (E. coli)
References: UniProt: Q99640, non-specific serine/threonine protein kinase

-
Non-polymers , 5 types, 113 molecules

#2: Chemical ChemComp-SO4 / SULFATE ION


Mass: 96.063 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: SO4
#3: Chemical ChemComp-QGI / (1P)-2-amino-1-(3-hydroxy-2,6-dimethylphenyl)-5,6-dimethyl-1H-pyrrolo[2,3-b]pyridine-3-carboxamide


Mass: 324.377 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C18H20N4O2 / Feature type: SUBJECT OF INVESTIGATION
#4: Chemical ChemComp-GOL / GLYCEROL / GLYCERIN / PROPANE-1,2,3-TRIOL


Mass: 92.094 Da / Num. of mol.: 3 / Source method: obtained synthetically / Formula: C3H8O3
#5: Chemical
ChemComp-EDO / 1,2-ETHANEDIOL / ETHYLENE GLYCOL


Mass: 62.068 Da / Num. of mol.: 12 / Source method: obtained synthetically / Formula: C2H6O2
#6: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 94 / Source method: isolated from a natural source / Formula: H2O

-
Details

Has ligand of interestY

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 2.78 Å3/Da / Density % sol: 55.8 %
Crystal growTemperature: 293 K / Method: vapor diffusion, hanging drop / pH: 8.25
Details: 5.6 to 6.6% PEG3350, 0.2 M Na2SO4, 0.1 M Tris-HCl and 10% EG
Temp details: 277K for 1 day and then 293K for a week

-
Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: APS / Beamline: 24-ID-C / Wavelength: 0.9792 Å
DetectorType: DECTRIS EIGER X 16M / Detector: PIXEL / Date: Sep 3, 2020
RadiationMonochromator: Si(111) / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.9792 Å / Relative weight: 1
ReflectionResolution: 2.15→47.82 Å / Num. obs: 40791 / % possible obs: 86.6 % / Redundancy: 1.997 % / Biso Wilson estimate: 72.702 Å2 / CC1/2: 1 / Rmerge(I) obs: 0.021 / Rrim(I) all: 0.029 / Χ2: 0.872 / Net I/σ(I): 16.97 / Num. measured all: 144392
Reflection shell

Diffraction-ID: 1

Resolution (Å)Redundancy (%)Rmerge(I) obsMean I/σ(I) obsNum. measured obsNum. possibleNum. unique obsCC1/2Rrim(I) all% possible all
2.15-2.282.0811.0320.752356313449113240.3561.40884.2
2.28-2.432.0230.4841.572214112732109460.7090.66186
2.43-2.631.9620.243.211972711765100560.9130.32885.5
2.63-2.882.0660.1127.04197591084895650.980.15488.2
2.88-3.222.0050.05114.817283983586200.9950.0787.6
3.22-3.711.8790.02330.5813903867573980.9990.03185.3
3.71-4.541.9920.01448.5913044733365480.9990.01989.3
4.54-6.391.9220.01353.019748570550730.9990.01988.9
6.39-47.821.8950.0158.145224317727570.9990.01486.8

-
Processing

Software
NameVersionClassification
XSCALEdata scaling
PHENIX1.19.2refinement
PDB_EXTRACT3.27data extraction
XDSdata reduction
PHENIXphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 3P1A

3p1a


Resolution: 2.15→47.82 Å / SU ML: 0.32 / Cross valid method: THROUGHOUT / σ(F): 1.35 / Phase error: 28.09 / Stereochemistry target values: ML
RfactorNum. reflection% reflection
Rfree0.2177 2036 4.99 %
Rwork0.19 38735 -
obs0.1915 40771 96.45 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL
Displacement parametersBiso max: 208.81 Å2 / Biso mean: 89.4569 Å2 / Biso min: 48.31 Å2
Refinement stepCycle: final / Resolution: 2.15→47.82 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms4178 0 124 94 4396
Biso mean--87.49 78.69 -
Num. residues----559
Refine LS restraints NCS
Ens-IDDom-IDAuth asym-IDNumberRefine-IDRmsType
11A2462X-RAY DIFFRACTION6.229TORSIONAL
12B2462X-RAY DIFFRACTION6.229TORSIONAL
LS refinement shell

Refine-ID: X-RAY DIFFRACTION / Rfactor Rfree error: 0 / Total num. of bins used: 15

Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkNum. reflection all% reflection obs (%)
2.15-2.20.37131260.34932431255792
2.2-2.250.36471370.33332577271497
2.25-2.310.3361360.29772605274197
2.31-2.380.30511360.27292566270297
2.38-2.460.30141330.262611274497
2.46-2.550.2821330.23852482261594
2.55-2.650.26931350.21972583271897
2.65-2.770.26381370.21232603274097
2.77-2.910.24581410.23042644278598
2.91-3.10.27371340.23912582271697
3.1-3.330.2331410.21572625276698
3.34-3.670.2441330.19872548268195
3.67-4.20.2261370.1692619275698
4.2-5.290.17991380.1622642278098
5.29-47.820.16711390.16162617275695
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)
10.235-0.2256-0.38541.08661.58152.3109-0.33630.090.00720.2929-0.6760.4095-0.1311-1.0479-1.29980.64170.0526-0.35921.1179-0.21671.3509-11.807-17.6179-0.5879
20.2538-0.10020.45780.129-0.26140.9228-0.67580.06860.4508-1.1865-0.3221.5373-1.0533-0.3259-0.75040.97260.1392-0.54690.6276-0.15261.4742-0.145-6.15642.9604
31.73811.4620.70721.22980.35742.56-0.3227-0.17350.2653-0.2814-0.33150.5777-0.3048-0.222-0.89130.60070.0149-0.13490.6699-0.08980.8096-0.1763-18.58723.7125
40.266-0.08040.6782.85180.88271.6439-0.0975-0.2340.15220.7452-0.34280.78930.1623-0.2863-0.01060.6608-0.04090.07350.6523-0.09680.67616.9456-14.765318.6006
52.09970.04821.49280.9865-1.21162.8066-0.00680.4936-0.5980.0662-0.15030.09261.1396-0.40840.25591.0653-0.09040.02010.6477-0.07870.92128.4124-30.37311.1608
60.4612-0.28850.0620.2785-0.13080.0819-0.21910.19760.07390.60050.1082-0.28240.39150.208500.91810.0233-0.02180.69770.02030.568720.009-24.584418.6883
70.4940.0171-0.29010.4136-0.0040.16710.1204-0.15330.01560.41640.0698-1.16370.02510.6083-0.00250.88010.048-0.15020.7658-0.02780.775529.7322-19.34222.0883
80.99011.02590.13621.44870.63210.81660.0685-0.4277-0.35191.3792-0.0821-0.63580.45060.4469-0.00731.2579-0.03740.03960.7493-0.00320.554917.9739-24.991132.1132
92.10620.72232.04540.25310.71822.0016-0.79160.5631-0.4137-0.793-0.7827-0.5961.24530.9003-3.33511.44630.46570.93231.04920.33511.472435.924812.4968-4.632
102.2632-0.94080.60910.4561-0.39866.0761-0.72880.2362-0.1031-1.6116-0.5892-1.31241.2962-0.3188-4.66761.20170.22840.50050.44020.10541.047124.31354.82711.8471
110.34480.5960.52333.8641-1.52112.7879-0.4905-0.3502-0.4401-1.39040.1698-0.20851.0274-0.3005-0.28070.72730.01060.12190.73980.02520.711823.104522.0236-1.1939
121.23090.7884-2.07291.2094-0.60014.1411-0.45-0.5432-0.6425-0.8792-0.5057-1.65170.07551.43070.09590.82160.18040.30650.86150.23340.992228.102814.19836.2143
131.3012-0.79680.17822.70230.4070.94690.14780.0345-0.12050.0478-0.1617-0.06860.09-0.08310.00010.61170.0318-0.02320.64140.03960.557315.051615.380516.7832
141.75540.3581-0.1570.15230.26211.308-0.29530.12190.37630.01320.47220.2435-1.0815-0.47040.15880.85920.1077-0.04630.74070.01490.6155.043928.23712.2747
150.4297-0.4204-0.25360.46360.34480.37970.24050.2226-0.15450.0828-0.08260.3610.2427-0.2553-0.00040.6210.07450.06120.79710.06770.6160.811519.940718.2396
160.7756-1.47840.22824.3032-1.83361.3716-0.1878-0.2458-0.36611.44510.6090.8670.0783-0.6870.19781.0968-0.04660.24420.96640.1650.7550.298316.647229.399
171.0166-0.3940.38841.6756-1.14331.0248-0.0994-0.58780.49111.5732-0.27320.3027-0.4653-0.036-0.05641.0197-0.002-0.02160.80490.04090.519611.22325.432729.0817
Refinement TLS group
IDRefine-IDRefine TLS-IDSelection detailsAuth asym-IDAuth seq-ID
1X-RAY DIFFRACTION1chain 'B' and (resid 77 through 104 )B77 - 104
2X-RAY DIFFRACTION2chain 'B' and (resid 105 through 129 )B105 - 129
3X-RAY DIFFRACTION3chain 'B' and (resid 130 through 164 )B130 - 164
4X-RAY DIFFRACTION4chain 'B' and (resid 165 through 249 )B165 - 249
5X-RAY DIFFRACTION5chain 'B' and (resid 250 through 269 )B250 - 269
6X-RAY DIFFRACTION6chain 'B' and (resid 270 through 301 )B270 - 301
7X-RAY DIFFRACTION7chain 'B' and (resid 302 through 329 )B302 - 329
8X-RAY DIFFRACTION8chain 'B' and (resid 330 through 361 )B330 - 361
9X-RAY DIFFRACTION9chain 'A' and (resid 77 through 109 )A77 - 109
10X-RAY DIFFRACTION10chain 'A' and (resid 110 through 140 )A110 - 140
11X-RAY DIFFRACTION11chain 'A' and (resid 141 through 164 )A141 - 164
12X-RAY DIFFRACTION12chain 'A' and (resid 165 through 188 )A165 - 188
13X-RAY DIFFRACTION13chain 'A' and (resid 189 through 270 )A189 - 270
14X-RAY DIFFRACTION14chain 'A' and (resid 271 through 284 )A271 - 284
15X-RAY DIFFRACTION15chain 'A' and (resid 285 through 321 )A285 - 321
16X-RAY DIFFRACTION16chain 'A' and (resid 322 through 339 )A322 - 339
17X-RAY DIFFRACTION17chain 'A' and (resid 340 through 361 )A340 - 361

+
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