[English] 日本語
Yorodumi
- PDB-6paf: Co-crystal Structure of human SMYD3 with Isoxazole Amides Inhibitors -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 6paf
TitleCo-crystal Structure of human SMYD3 with Isoxazole Amides Inhibitors
ComponentsHistone-lysine N-methyltransferase SMYD3
KeywordsTRANSFERASE/TRANSFERASE INHIBITOR / methyltransferase / oncology / inhibitor / TRANSFERASE / TRANSFERASE-TRANSFERASE INHIBITOR complex
Function / homology
Function and homology information


histone H3K36 dimethyltransferase activity / histone H4 methyltransferase activity / [histone H3]-lysine4 N-trimethyltransferase / myotube cell development / histone H3K4 trimethyltransferase activity / RNA polymerase II intronic transcription regulatory region sequence-specific DNA binding / RNA polymerase II complex binding / cellular response to dexamethasone stimulus / establishment of protein localization / PKMTs methylate histone lysines ...histone H3K36 dimethyltransferase activity / histone H4 methyltransferase activity / [histone H3]-lysine4 N-trimethyltransferase / myotube cell development / histone H3K4 trimethyltransferase activity / RNA polymerase II intronic transcription regulatory region sequence-specific DNA binding / RNA polymerase II complex binding / cellular response to dexamethasone stimulus / establishment of protein localization / PKMTs methylate histone lysines / nucleosome assembly / positive regulation of peptidyl-serine phosphorylation / methylation / RNA polymerase II cis-regulatory region sequence-specific DNA binding / positive regulation of transcription by RNA polymerase II / nucleoplasm / nucleus / metal ion binding / cytosol
Similarity search - Function
Histone-lysine N-methyltransferase Smyd3 / SMYD3, SET domain / Histone-lysine N-methyltransferase (EC 2.1.1.43) family profile. / MYND finger / Zinc finger, MYND-type / Zinc finger MYND-type signature. / Zinc finger MYND-type profile. / SET (Su(var)3-9, Enhancer-of-zeste, Trithorax) domain / SET domain superfamily / SET domain ...Histone-lysine N-methyltransferase Smyd3 / SMYD3, SET domain / Histone-lysine N-methyltransferase (EC 2.1.1.43) family profile. / MYND finger / Zinc finger, MYND-type / Zinc finger MYND-type signature. / Zinc finger MYND-type profile. / SET (Su(var)3-9, Enhancer-of-zeste, Trithorax) domain / SET domain superfamily / SET domain / SET domain profile. / SET domain / Tetratricopeptide-like helical domain superfamily
Similarity search - Domain/homology
Chem-O6A / S-ADENOSYLMETHIONINE / Histone-lysine N-methyltransferase SMYD3
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.241 Å
AuthorsElkins, P.A. / Wang, L.
CitationJournal: Acs Med.Chem.Lett. / Year: 2020
Title: Discovery of Isoxazole Amides as Potent and Selective SMYD3 Inhibitors.
Authors: Su, D.S. / Qu, J. / Schulz, M. / Blackledge, C.W. / Yu, H. / Zeng, J. / Burgess, J. / Reif, A. / Stern, M. / Nagarajan, R. / Pappalardi, M.B. / Wong, K. / Graves, A.P. / Bonnette, W. / Wang, ...Authors: Su, D.S. / Qu, J. / Schulz, M. / Blackledge, C.W. / Yu, H. / Zeng, J. / Burgess, J. / Reif, A. / Stern, M. / Nagarajan, R. / Pappalardi, M.B. / Wong, K. / Graves, A.P. / Bonnette, W. / Wang, L. / Elkins, P. / Knapp-Reed, B. / Carson, J.D. / McHugh, C. / Mohammad, H. / Kruger, R. / Luengo, J. / Heerding, D.A. / Creasy, C.L.
History
DepositionJun 11, 2019Deposition site: RCSB / Processing site: RCSB
Revision 1.0Jan 15, 2020Provider: repository / Type: Initial release
Revision 1.1Mar 11, 2020Group: Database references / Category: citation / citation_author
Item: _citation.journal_volume / _citation.page_first ..._citation.journal_volume / _citation.page_first / _citation.page_last / _citation.pdbx_database_id_DOI / _citation.pdbx_database_id_PubMed / _citation.title / _citation.year / _citation_author.name
Revision 1.2Oct 11, 2023Group: Data collection / Database references ...Data collection / Database references / Derived calculations / Refinement description
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / database_2 / pdbx_initial_refinement_model / pdbx_struct_conn_angle / struct_conn
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession ..._database_2.pdbx_DOI / _database_2.pdbx_database_accession / _pdbx_struct_conn_angle.ptnr1_auth_seq_id / _pdbx_struct_conn_angle.ptnr1_symmetry / _pdbx_struct_conn_angle.ptnr3_auth_seq_id / _pdbx_struct_conn_angle.ptnr3_symmetry / _pdbx_struct_conn_angle.value / _struct_conn.pdbx_dist_value / _struct_conn.ptnr1_auth_seq_id / _struct_conn.ptnr1_label_asym_id / _struct_conn.ptnr2_auth_seq_id / _struct_conn.ptnr2_symmetry

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Histone-lysine N-methyltransferase SMYD3
hetero molecules


Theoretical massNumber of molelcules
Total (without water)50,77410
Polymers49,5431
Non-polymers1,2329
Water8,773487
1


  • Idetical with deposited unit
  • defined by author&software
  • Evidence: gel filtration
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
Unit cell
Length a, b, c (Å)60.971, 65.991, 106.544
Angle α, β, γ (deg.)90.000, 90.000, 90.000
Int Tables number19
Space group name H-MP212121

-
Components

-
Protein , 1 types, 1 molecules A

#1: Protein Histone-lysine N-methyltransferase SMYD3 / SET and MYND domain-containing protein 3 / Zinc finger MYND domain-containing protein 1


Mass: 49542.520 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: SMYD3, ZMYND1, ZNFN3A1 / Cell line (production host): Sf9 / Production host: unidentified baculovirus
References: UniProt: Q9H7B4, histone-lysine N-methyltransferase

-
Non-polymers , 6 types, 496 molecules

#2: Chemical ChemComp-ZN / ZINC ION


Mass: 65.409 Da / Num. of mol.: 3 / Source method: obtained synthetically / Formula: Zn
#3: Chemical ChemComp-MG / MAGNESIUM ION


Mass: 24.305 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: Mg
#4: Chemical ChemComp-GOL / GLYCEROL / GLYCERIN / PROPANE-1,2,3-TRIOL


Mass: 92.094 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C3H8O3
#5: Chemical ChemComp-SAM / S-ADENOSYLMETHIONINE


Mass: 398.437 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C15H22N6O5S
#6: Chemical ChemComp-O6A / N-(1-{[4-(aminomethyl)phenyl]sulfonyl}piperidin-4-yl)-5-cyclopropyl-1,2-oxazole-3-carboxamide


Mass: 404.483 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C19H24N4O4S / Feature type: SUBJECT OF INVESTIGATION
#7: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 487 / 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: 2.16 Å3/Da / Density % sol: 43.14 %
Crystal growTemperature: 295 K / Method: vapor diffusion, hanging drop
Details: Sitting Drop, Linbro tray, room temp, reservoir is 10% PEG 3350, 0.2M MgOAc , protein:reservoir is 1:1, streak seed soaking: 2ul 20%PEG 3350, 0.4M MgOAc added to 2ul protein, mix and add 0. ...Details: Sitting Drop, Linbro tray, room temp, reservoir is 10% PEG 3350, 0.2M MgOAc , protein:reservoir is 1:1, streak seed soaking: 2ul 20%PEG 3350, 0.4M MgOAc added to 2ul protein, mix and add 0.3ul to drop, store at 295

-
Data collection

DiffractionMean temperature: 295 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: APS / Beamline: 21-ID-D / Wavelength: 1.07805 Å
DetectorType: MARMOSAIC 300 mm CCD / Detector: CCD / Date: Aug 5, 2015
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1.07805 Å / Relative weight: 1
ReflectionResolution: 1.24→50 Å / Num. obs: 118748 / % possible obs: 97 % / Redundancy: 4.8 % / Rmerge(I) obs: 0.072 / Rpim(I) all: 0.036 / Rrim(I) all: 0.081 / Χ2: 1.054 / Net I/σ(I): 12.4 / Num. measured all: 571090
Reflection shell

Diffraction-ID: 1

Resolution (Å)Redundancy (%)Rmerge(I) obsNum. unique obsCC1/2Rpim(I) allRrim(I) allΧ2% possible all
1.24-1.284.80.417109160.8750.2070.4681.00390.5
1.28-1.344.90.334116840.9120.1650.3741.09196.3
1.34-1.44.90.257117120.9470.1260.2881.06196.8
1.4-1.474.90.198118190.9670.0970.2211.06397.3
1.47-1.564.90.156118670.9790.0760.1741.0697.7
1.56-1.684.90.12119580.9860.0580.1341.06298.2
1.68-1.854.90.093120320.990.0450.1031.05598.5
1.85-2.124.80.074121300.9930.0370.0831.06598.9
2.12-2.674.70.061122340.9940.030.0681.03298.9
2.67-504.40.054123960.9950.0280.0611.04197.1

-
Processing

Software
NameVersionClassification
PHENIX1.16-3549refinement
XDSdata reduction
Aimlessdata scaling
PDB_EXTRACT3.25data extraction
PHENIXphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 5HI7

5hi7


Resolution: 1.241→32.995 Å / SU ML: 0.11 / Cross valid method: THROUGHOUT / σ(F): 1.36 / Phase error: 18.13 / Stereochemistry target values: ML
RfactorNum. reflection% reflectionSelection details
Rfree0.1875 8461 7.13 %RANDOM
Rwork0.1718 110230 --
obs0.1729 118691 97.46 %-
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL
Displacement parametersBiso max: 59.36 Å2 / Biso mean: 17.3398 Å2 / Biso min: 5.91 Å2
Refinement stepCycle: final / Resolution: 1.241→32.995 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms3311 0 72 492 3875
Biso mean--12.13 25.78 -
Num. residues----423
LS refinement shell

Refine-ID: X-RAY DIFFRACTION / Rfactor Rfree error: 0

Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection Rwork% reflection obs (%)
1.2412-1.25530.25882620.2439338592
1.2553-1.27010.22492800.2252360596
1.2701-1.28560.22732620.2194356996
1.2856-1.30190.2352720.2142359296
1.3019-1.3190.23012860.2058360296
1.319-1.33710.22632700.2069359597
1.3371-1.35620.22542750.1996362097
1.3562-1.37640.22232600.1984362897
1.3764-1.39790.21562910.1888359497
1.3979-1.42080.19592540.1935368697
1.4208-1.44530.20722680.1868362297
1.4453-1.47160.21472790.1826365398
1.4716-1.49990.19332940.1751365097
1.4999-1.53050.19252830.1721367598
1.5305-1.56380.18812670.1731364798
1.5638-1.60020.17722850.1668368498
1.6002-1.64020.20972780.1689369598
1.6402-1.68450.18222790.1664369898
1.6845-1.73410.18333180.1623367699
1.7341-1.79010.19033110.1686368299
1.7901-1.85410.20353100.1659367799
1.8541-1.92830.17332730.1689374399
1.9283-2.0160.17992770.1723376899
2.016-2.12230.17623220.1643368699
2.1223-2.25520.17482680.1597378299
2.2552-2.42930.18012350.1645382699
2.4293-2.67370.17722980.1721376399
2.6737-3.06030.1842920.1775378898
3.0603-3.85480.18252910.1629382098
3.8548-500.1733210.1573381995
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)
10.550.0175-0.25841.0768-0.06312.42830.0238-0.10840.0550.30590.07840.118-0.20920.234-0.07310.1363-0.00670.04880.1208-0.00160.14719.882-3.382-4.547
21.0442-0.4981-0.18971.1980.27831.3147-0.0559-0.1709-0.04410.20150.06420.05170.0979-0.015-0.01050.0746-0.00190.01650.09770.01220.070114.475-17.588-5.615
30.67030.4759-0.27631.0335-0.17170.40960.0758-0.0590.09520.1143-0.02870.0748-0.09620.0272-0.02850.08390.00170.01230.06910.00780.065222.4827.707-18.717
Refinement TLS group
IDRefine-IDRefine TLS-IDSelection detailsAuth asym-IDAuth seq-ID
1X-RAY DIFFRACTION1( CHAIN A AND RESID 3:93 )A3 - 93
2X-RAY DIFFRACTION2( CHAIN A AND RESID 96:186 )A96 - 186
3X-RAY DIFFRACTION3( CHAIN A AND RESID 187:428 )A187 - 428

+
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