[English] 日本語
Yorodumi
- PDB-6dq9: Linked KDM5A JMJ Domain Bound to the Covalent Inhibitor N69 i.e. ... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 6dq9
TitleLinked KDM5A JMJ Domain Bound to the Covalent Inhibitor N69 i.e. [2-((3-acrylamidophenyl)(2-(piperidin-1-yl)ethoxy)methyl)thieno[3,2-b]pyridine-7-carboxylic acid]
ComponentsLinked KDM5A Jmj Domain
KeywordsOXIDOREDUCTASE/INHIBITOR / DEMETHYLASE INHIBITION / OXIDOREDUCTASE-INHIBITOR complex
Function / homology
Function and homology information


facultative heterochromatin formation / [histone H3]-trimethyl-L-lysine4 demethylase / histone H3K4me/H3K4me2/H3K4me3 demethylase activity / regulation of DNA-binding transcription factor activity / enzyme inhibitor activity / histone demethylase activity / Chromatin modifications during the maternal to zygotic transition (MZT) / circadian regulation of gene expression / HDMs demethylate histones / chromatin DNA binding ...facultative heterochromatin formation / [histone H3]-trimethyl-L-lysine4 demethylase / histone H3K4me/H3K4me2/H3K4me3 demethylase activity / regulation of DNA-binding transcription factor activity / enzyme inhibitor activity / histone demethylase activity / Chromatin modifications during the maternal to zygotic transition (MZT) / circadian regulation of gene expression / HDMs demethylate histones / chromatin DNA binding / histone binding / transcription coactivator activity / transcription cis-regulatory region binding / chromatin remodeling / regulation of DNA-templated transcription / chromatin / nucleolus / positive regulation of DNA-templated transcription / negative regulation of transcription by RNA polymerase II / DNA binding / zinc ion binding / nucleoplasm / nucleus
Similarity search - Function
: / : / : / : / Lysine-specific demethylase-like domain / : / PLU-1-like protein / Lysine-specific demethylase 5, C-terminal helical domain / Zinc finger, C5HC2-type / C5HC2 zinc finger ...: / : / : / : / Lysine-specific demethylase-like domain / : / PLU-1-like protein / Lysine-specific demethylase 5, C-terminal helical domain / Zinc finger, C5HC2-type / C5HC2 zinc finger / ARID DNA-binding domain / ARID DNA-binding domain superfamily / ARID/BRIGHT DNA binding domain / ARID domain profile. / BRIGHT, ARID (A/T-rich interaction domain) domain / ARID/BRIGHT DNA binding domain / JmjN domain / jmjN domain / JmjN domain profile. / Small domain found in the jumonji family of transcription factors / Cupin / JmjC domain, hydroxylase / A domain family that is part of the cupin metalloenzyme superfamily. / JmjC domain / JmjC domain profile. / Zinc finger, PHD-type, conserved site / PHD-finger / Zinc finger PHD-type signature. / Zinc finger PHD-type profile. / Zinc finger, PHD-finger / Zinc finger, PHD-type / PHD zinc finger / Zinc finger, FYVE/PHD-type / Zinc finger, RING/FYVE/PHD-type / Jelly Rolls / Sandwich / Mainly Beta
Similarity search - Domain/homology
Chem-H74 / : / Lysine-specific demethylase 5A
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.748 Å
AuthorsHorton, J.R. / Cheng, X.
Funding support United States, 1items
OrganizationGrant numberCountry
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)GM049245-23 United States
Citation
Journal: J. Med. Chem. / Year: 2018
Title: Structure-Based Engineering of Irreversible Inhibitors against Histone Lysine Demethylase KDM5A.
Authors: Horton, J.R. / Woodcock, C.B. / Chen, Q. / Liu, X. / Zhang, X. / Shanks, J. / Rai, G. / Mott, B.T. / Jansen, D.J. / Kales, S.C. / Henderson, M.J. / Cyr, M. / Pohida, K. / Hu, X. / Shah, P. / ...Authors: Horton, J.R. / Woodcock, C.B. / Chen, Q. / Liu, X. / Zhang, X. / Shanks, J. / Rai, G. / Mott, B.T. / Jansen, D.J. / Kales, S.C. / Henderson, M.J. / Cyr, M. / Pohida, K. / Hu, X. / Shah, P. / Xu, X. / Jadhav, A. / Maloney, D.J. / Hall, M.D. / Simeonov, A. / Fu, H. / Vertino, P.M. / Cheng, X.
#1: Journal: Cell Chem Biol / Year: 2016
Title: Structural Basis for KDM5A Histone Lysine Demethylase Inhibition by Diverse Compounds.
Authors: Horton, J.R. / Liu, X. / Gale, M. / Wu, L. / Shanks, J.R. / Zhang, X. / Webber, P.J. / Bell, J.S. / Kales, S.C. / Mott, B.T. / Rai, G. / Jansen, D.J. / Henderson, M.J. / Urban, D.J. / Hall, ...Authors: Horton, J.R. / Liu, X. / Gale, M. / Wu, L. / Shanks, J.R. / Zhang, X. / Webber, P.J. / Bell, J.S. / Kales, S.C. / Mott, B.T. / Rai, G. / Jansen, D.J. / Henderson, M.J. / Urban, D.J. / Hall, M.D. / Simeonov, A. / Maloney, D.J. / Johns, M.A. / Fu, H. / Jadhav, A. / Vertino, P.M. / Yan, Q. / Cheng, X.
#2: Journal: J. Biol. Chem. / Year: 2016
Title: Characterization of a Linked Jumonji Domain of the KDM5/JARID1 Family of Histone H3 Lysine 4 Demethylases.
Authors: Horton, J.R. / Engstrom, A. / Zoeller, E.L. / Liu, X. / Shanks, J.R. / Zhang, X. / Johns, M.A. / Vertino, P.M. / Fu, H. / Cheng, X.
#3: Journal: J. Med. Chem. / Year: 2018
Title: Insights into the Action of Inhibitor Enantiomers against Histone Lysine Demethylase 5A.
Authors: Horton, J.R. / Liu, X. / Wu, L. / Zhang, K. / Shanks, J. / Zhang, X. / Rai, G. / Mott, B.T. / Jansen, D.J. / Kales, S.C. / Henderson, M.J. / Pohida, K. / Fang, Y. / Hu, X. / Jadhav, A. / ...Authors: Horton, J.R. / Liu, X. / Wu, L. / Zhang, K. / Shanks, J. / Zhang, X. / Rai, G. / Mott, B.T. / Jansen, D.J. / Kales, S.C. / Henderson, M.J. / Pohida, K. / Fang, Y. / Hu, X. / Jadhav, A. / Maloney, D.J. / Hall, M.D. / Simeonov, A. / Fu, H. / Vertino, P.M. / Yan, Q. / Cheng, X.
History
DepositionJun 10, 2018Deposition site: RCSB / Processing site: RCSB
Revision 1.0Nov 21, 2018Provider: repository / Type: Initial release
Revision 1.1May 1, 2019Group: Data collection / Database references / Category: citation / citation_author
Item: _citation.journal_volume / _citation.page_first ..._citation.journal_volume / _citation.page_first / _citation.page_last / _citation.title / _citation_author.identifier_ORCID
Revision 1.2Jan 1, 2020Group: Author supporting evidence / Category: pdbx_audit_support / Item: _pdbx_audit_support.funding_organization
Revision 1.3Oct 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.ptnr3_auth_seq_id / _pdbx_struct_conn_angle.value / _struct_conn.pdbx_dist_value / _struct_conn.ptnr2_auth_seq_id

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Linked KDM5A Jmj Domain
hetero molecules


Theoretical massNumber of molelcules
Total (without water)38,8388
Polymers37,9451
Non-polymers8937
Water3,765209
1


  • Idetical with deposited unit
  • defined by author&software
  • Evidence: gel filtration
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area1310 Å2
ΔGint7 kcal/mol
Surface area14090 Å2
MethodPISA
Unit cell
Length a, b, c (Å)117.517, 62.001, 46.725
Angle α, β, γ (deg.)90.00, 92.13, 90.00
Int Tables number5
Space group name H-MC121
Components on special symmetry positions
IDModelComponents
11A-886-

HOH

-
Components

-
Protein , 1 types, 1 molecules A

#1: Protein Linked KDM5A Jmj Domain / Histone demethylase JARID1A / Jumonji/ARID domain-containing protein 1A / Retinoblastoma-binding ...Histone demethylase JARID1A / Jumonji/ARID domain-containing protein 1A / Retinoblastoma-binding protein 2 / RBBP-2


Mass: 37944.836 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: KDM5A, JARID1A, RBBP2, RBP2 / Production host: Escherichia coli (E. coli) / Strain (production host): BL21(DE3) / Variant (production host): GOLD C-PLUS
References: UniProt: P29375, Oxidoreductases; Acting on paired donors, with incorporation or reduction of molecular oxygen; With 2-oxoglutarate as one donor, and incorporation of one atom of oxygen into each donor

-
Non-polymers , 6 types, 216 molecules

#2: Chemical ChemComp-H74 / 2-{(R)-[3-(acryloylamino)phenyl][2-(piperidin-1-yl)ethoxy]methyl}thieno[3,2-b]pyridine-7-carboxylic acid


Mass: 465.565 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C25H27N3O4S / Feature type: SUBJECT OF INVESTIGATION
#3: Chemical ChemComp-MN / MANGANESE (II) ION


Mass: 54.938 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: Mn
#4: Chemical ChemComp-GOL / GLYCEROL / GLYCERIN / PROPANE-1,2,3-TRIOL


Mass: 92.094 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C3H8O3
#5: Chemical ChemComp-DMS / DIMETHYL SULFOXIDE


Mass: 78.133 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C2H6OS / Comment: DMSO, precipitant*YM
#6: Chemical ChemComp-EDO / 1,2-ETHANEDIOL / ETHYLENE GLYCOL


Mass: 62.068 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C2H6O2
#7: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 209 / Source method: isolated from a natural source / Formula: H2O

-
Details

Nonpolymer detailsInhibitor N69 (PDB chemical component H74) makes a covalent bond to C481 of KDM5A. There is an ...Inhibitor N69 (PDB chemical component H74) makes a covalent bond to C481 of KDM5A. There is an apparent loss of a carbon before the bond is formed.

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 2.24 Å3/Da / Density % sol: 45.13 %
Crystal growTemperature: 289 K / Method: vapor diffusion, sitting drop
Details: 1.2-1.35 M (NH4)2SO4, 0.1 M Tris-HCl (pH 8.6-9.2) 0-20% glycerol 25 mM (Na/K) dibasic/monobasic phosphate
PH range: 8.6-9.2

-
Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: SYNCHROTRON / Site: APS / Beamline: 22-BM / Wavelength: 1 Å
DetectorType: RAYONIX MX-300 / Detector: CCD / Date: Oct 16, 2016
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1 Å / Relative weight: 1
ReflectionResolution: 1.748→33.11 Å / Num. obs: 34013 / % possible obs: 100 % / Redundancy: 4.4 % / Rmerge(I) obs: 0.084 / Rpim(I) all: 0.045 / Net I/σ(I): 18
Reflection shellResolution: 1.748→1.81 Å / Redundancy: 4.1 % / Rmerge(I) obs: 0.794 / Mean I/σ(I) obs: 2 / Num. unique obs: 3382 / CC1/2: 0.733 / Rpim(I) all: 0.442 / % possible all: 100

-
Processing

Software
NameVersionClassification
PHENIX(1.13_2998: ???)refinement
HKL-2000data reduction
HKL-2000data scaling
PHENIXphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 5IVB

5ivb


Resolution: 1.748→33.1 Å / SU ML: 0.17 / Cross valid method: THROUGHOUT / σ(F): 1.35 / Phase error: 20.17 / Stereochemistry target values: ML
RfactorNum. reflection% reflection
Rfree0.1983 1669 4.91 %
Rwork0.1735 --
obs0.1747 34011 99.78 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL
Refinement stepCycle: LAST / Resolution: 1.748→33.1 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms2358 0 55 209 2622
Refine LS restraints
Refine-IDTypeDev idealNumber
X-RAY DIFFRACTIONf_bond_d0.0022522
X-RAY DIFFRACTIONf_angle_d0.5253448
X-RAY DIFFRACTIONf_dihedral_angle_d3.7691983
X-RAY DIFFRACTIONf_chiral_restr0.043356
X-RAY DIFFRACTIONf_plane_restr0.004449
LS refinement shell
Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkRefine-ID% reflection obs (%)
1.7475-1.79890.25441510.2562617X-RAY DIFFRACTION97
1.7989-1.8570.26231290.23772675X-RAY DIFFRACTION100
1.857-1.92340.27631300.21862663X-RAY DIFFRACTION100
1.9234-2.00040.22481300.19552732X-RAY DIFFRACTION100
2.0004-2.09140.18651560.17652655X-RAY DIFFRACTION100
2.0914-2.20160.19141400.17782691X-RAY DIFFRACTION100
2.2016-2.33950.20591280.17612722X-RAY DIFFRACTION100
2.3395-2.52010.21681490.18172661X-RAY DIFFRACTION100
2.5201-2.77360.22541470.18292723X-RAY DIFFRACTION100
2.7736-3.17470.2046690.16572766X-RAY DIFFRACTION100
3.1747-3.99860.19031610.1512693X-RAY DIFFRACTION100
3.9986-33.1060.16451790.15392744X-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)
10.01960.02780.07170.04080.06950.07730.02920.01340.04280.14450.0595-0.02590.18530.026800.15160.026-0.00860.1421-0.00770.1887-18.98911.65939.2239
20.10830.0473-0.1240.1075-0.08430.1912-0.03380.03590.00710.00490.0181-0.0354-0.05080.0417-00.1335-0.016-0.01930.1554-0.0080.1843-18.349413.46458.1195
30.0182-0.0053-0.02250.03830.0090.0214-0.0535-0.11710.14420.09940.04890.059-0.1136-0.04360.00430.18560.0074-0.01270.1042-0.0150.1327-28.711227.534420.518
40.0209-0.01580.00650.02630.00410.0188-0.09290.0186-0.01860.1714-0.02010.04130.1824-0.177-0.01170.1718-0.01520.02640.14250.00810.0962-33.048212.670222.3812
50.012-0.03690.02270.0750.06510.08350.01490.02340.0191-0.0240.0729-0.0219-0.3236-0.04070.01980.1094-0.07790.04480.1099-0.03980.1906-17.748724.810311.5071
60.03420.0203-0.06930.036-0.0220.01980.18920.0474-0.0643-0.48220.14150.0114-0.26130.15750.0111-0.1546-0.04820.09290.3414-0.04410.2207-5.498316.32691.0029
70.0445-0.0067-0.02230.07340.01320.051-0.03170.00770.05230.00890.0249-0.00930.01280.003-00.1326-0.0217-0.00520.13310.00160.1103-23.001315.58366.539
80.00470.001-0.00320.0065-0.00520.0039-0.03160.14210.0784-0.05080.0780.02920.048-0.043100.1808-0.034-0.03370.1996-0.01450.1916-37.51589.4354-5.136
9-0.0082-0.0081-0.00410.0107-0.014-0.02690.0694-0.065-0.0409-0.0489-0.0783-0.0682-0.1103-0.1523-00.2429-0.0030.03940.18810.0150.2371-38.87316.80560.0297
100.0458-0.0313-0.03220.1075-0.03850.0522-0.02980.034-0.0089-0.01090.0509-0.03050.030.0167-0.00010.1366-0.02570.00010.135-0.00260.1181-22.930911.02456.1343
Refinement TLS group
IDRefine-IDRefine TLS-IDSelection details
1X-RAY DIFFRACTION1chain 'A' and (resid 11 through 31 )
2X-RAY DIFFRACTION2chain 'A' and (resid 32 through 81 )
3X-RAY DIFFRACTION3chain 'A' and (resid 82 through 378 )
4X-RAY DIFFRACTION4chain 'A' and (resid 379 through 399 )
5X-RAY DIFFRACTION5chain 'A' and (resid 400 through 432 )
6X-RAY DIFFRACTION6chain 'A' and (resid 433 through 469 )
7X-RAY DIFFRACTION7chain 'A' and (resid 470 through 507 )
8X-RAY DIFFRACTION8chain 'A' and (resid 508 through 521 )
9X-RAY DIFFRACTION9chain 'A' and (resid 522 through 547 )
10X-RAY DIFFRACTION10chain 'A' and (resid 548 through 588 )

+
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