[English] 日本語
Yorodumi
- PDB-6x9k: Human DNMT1(729-1600) Bound to Zebularine-Containing 12mer dsDNA ... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 6x9k
TitleHuman DNMT1(729-1600) Bound to Zebularine-Containing 12mer dsDNA and Inhibitor GSK3685032A
Components
  • DNA (5'-D(*GP*AP*GP*GP*CP*(5CM)P*GP*CP*CP*TP*GP*C)-3')
  • DNA (5'-D(*GP*CP*AP*GP*G)-R(P*(PYO))-D(P*GP*GP*CP*CP*TP*C)-3')
  • DNA (cytosine-5)-methyltransferase 1
KeywordsTRANSFERASE/TRANSFERASE INHIBITOR/DNA / EPIGENETICS / DNA METHYLTRANSFERASE FOLD / MAINTENANCE METHYLATION / INHIBITION / TRANSFERASE / TRANSFERASE-TRANSFERASE INHIBITOR complex / TRANSFERASE-TRANSFERASE INHIBITOR-DNA complex
Function / homology
Function and homology information


negative regulation of vascular associated smooth muscle cell differentiation involved in phenotypic switching / : / epigenetic programming of gene expression / cellular response to bisphenol A / negative regulation of vascular associated smooth muscle cell apoptotic process / DNA-methyltransferase activity / DNA (cytosine-5-)-methyltransferase / DNA (cytosine-5-)-methyltransferase activity / DNA methylation-dependent heterochromatin formation / SUMOylation of DNA methylation proteins ...negative regulation of vascular associated smooth muscle cell differentiation involved in phenotypic switching / : / epigenetic programming of gene expression / cellular response to bisphenol A / negative regulation of vascular associated smooth muscle cell apoptotic process / DNA-methyltransferase activity / DNA (cytosine-5-)-methyltransferase / DNA (cytosine-5-)-methyltransferase activity / DNA methylation-dependent heterochromatin formation / SUMOylation of DNA methylation proteins / negative regulation of gene expression via chromosomal CpG island methylation / female germ cell nucleus / methyl-CpG binding / pericentric heterochromatin / positive regulation of vascular associated smooth muscle cell proliferation / DNA methylation / replication fork / PRC2 methylates histones and DNA / Defective pyroptosis / promoter-specific chromatin binding / cellular response to amino acid stimulus / NoRC negatively regulates rRNA expression / negative regulation of gene expression / DNA-templated transcription / positive regulation of gene expression / negative regulation of transcription by RNA polymerase II / DNA binding / RNA binding / zinc ion binding / nucleoplasm / nucleus
Similarity search - Function
DNA (cytosine-5)-methyltransferase 1-like / DNA (cytosine-5)-methyltransferase 1, replication foci domain / Cytosine specific DNA methyltransferase replication foci domain / DMAP1-binding Domain / DMAP1-binding Domain / DMAP1-binding domain / DMAP1-binding domain profile. / DNA methylase, C-5 cytosine-specific, conserved site / C-5 cytosine-specific DNA methylases C-terminal signature. / DNA methylase, C-5 cytosine-specific, active site ...DNA (cytosine-5)-methyltransferase 1-like / DNA (cytosine-5)-methyltransferase 1, replication foci domain / Cytosine specific DNA methyltransferase replication foci domain / DMAP1-binding Domain / DMAP1-binding Domain / DMAP1-binding domain / DMAP1-binding domain profile. / DNA methylase, C-5 cytosine-specific, conserved site / C-5 cytosine-specific DNA methylases C-terminal signature. / DNA methylase, C-5 cytosine-specific, active site / C-5 cytosine-specific DNA methylases active site. / C-5 cytosine-specific DNA methylase (Dnmt) domain profile. / CXXC zinc finger domain / Zinc finger, CXXC-type / Zinc finger CXXC-type profile. / C-5 cytosine methyltransferase / C-5 cytosine-specific DNA methylase / Bromo adjacent homology (BAH) domain superfamily / Bromo adjacent homology domain / Bromo adjacent homology (BAH) domain / BAH domain / BAH domain profile. / S-adenosyl-L-methionine-dependent methyltransferase superfamily
Similarity search - Domain/homology
Chem-UXM / DNA / DNA (> 10) / DNA (cytosine-5)-methyltransferase 1
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / FOURIER SYNTHESIS / Resolution: 2.65 Å
AuthorsPathuri, S. / Horton, J.R. / Cheng, X.
Funding support United States, 1items
OrganizationGrant numberCountry
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)R35GM134744 United States
CitationJournal: Nat Cancer / Year: 2021
Title: Discovery of a first-in-class reversible DNMT1-selective inhibitor with improved tolerability and efficacy in acute myeloid leukemia.
Authors: Pappalardi, M.B. / Keenan, K. / Cockerill, M. / Kellner, W.A. / Stowell, A. / Sherk, C. / Wong, K. / Pathuri, S. / Briand, J. / Steidel, M. / Chapman, P. / Groy, A. / Wiseman, A.K. / McHugh, ...Authors: Pappalardi, M.B. / Keenan, K. / Cockerill, M. / Kellner, W.A. / Stowell, A. / Sherk, C. / Wong, K. / Pathuri, S. / Briand, J. / Steidel, M. / Chapman, P. / Groy, A. / Wiseman, A.K. / McHugh, C.F. / Campobasso, N. / Graves, A.P. / Fairweather, E. / Werner, T. / Raoof, A. / Butlin, R.J. / Rueda, L. / Horton, J.R. / Fosbenner, D.T. / Zhang, C. / Handler, J.L. / Muliaditan, M. / Mebrahtu, M. / Jaworski, J.P. / McNulty, D.E. / Burt, C. / Eberl, H.C. / Taylor, A.N. / Ho, T. / Merrihew, S. / Foley, S.W. / Rutkowska, A. / Li, M. / Romeril, S.P. / Goldberg, K. / Zhang, X. / Kershaw, C.S. / Bantscheff, M. / Jurewicz, A.J. / Minthorn, E. / Grandi, P. / Patel, M. / Benowitz, A.B. / Mohammad, H.P. / Gilmartin, A.G. / Prinjha, R.K. / Ogilvie, D. / Carpenter, C. / Heerding, D. / Baylin, S.B. / Jones, P.A. / Cheng, X. / King, B.W. / Luengo, J.I. / Jordan, A.M. / Waddell, I. / Kruger, R.G. / McCabe, M.T.
History
DepositionJun 2, 2020Deposition site: RCSB / Processing site: RCSB
Revision 1.0Jul 7, 2021Provider: repository / Type: Initial release
Revision 1.1Jan 19, 2022Group: Database references / Category: citation / citation_author / database_2
Item: _citation.country / _citation.journal_abbrev ..._citation.country / _citation.journal_abbrev / _citation.journal_id_CSD / _citation.journal_id_ISSN / _citation.journal_volume / _citation.page_first / _citation.page_last / _citation.pdbx_database_id_PubMed / _citation.title / _citation.year / _database_2.pdbx_DOI / _database_2.pdbx_database_accession
Revision 1.2Oct 18, 2023Group: Data collection / Refinement description
Category: chem_comp_atom / chem_comp_bond / pdbx_initial_refinement_model

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: DNA (cytosine-5)-methyltransferase 1
C: DNA (5'-D(*GP*AP*GP*GP*CP*(5CM)P*GP*CP*CP*TP*GP*C)-3')
D: DNA (5'-D(*GP*CP*AP*GP*G)-R(P*(PYO))-D(P*GP*GP*CP*CP*TP*C)-3')
hetero molecules


Theoretical massNumber of molelcules
Total (without water)107,25715
Polymers106,1473
Non-polymers1,11012
Water3,405189
1


  • Idetical with deposited unit
  • defined by author&software
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area6810 Å2
ΔGint4 kcal/mol
Surface area38750 Å2
MethodPISA
Unit cell
Length a, b, c (Å)161.318, 78.336, 117.068
Angle α, β, γ (deg.)90.000, 125.761, 90.000
Int Tables number5
Space group name H-MC121
Space group name HallC2y
Symmetry operation#1: x,y,z
#2: -x,y,-z
#3: x+1/2,y+1/2,z
#4: -x+1/2,y+1/2,-z

-
Components

-
Protein , 1 types, 1 molecules A

#1: Protein DNA (cytosine-5)-methyltransferase 1 / Dnmt1 / CXXC-type zinc finger protein 9 / DNA methyltransferase HsaI / M.HsaI / MCMT


Mass: 98803.555 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: DNMT1, AIM, CXXC9, DNMT
Production host: Escherichia coli 'BL21-Gold(DE3)pLysS AG' (bacteria)
References: UniProt: P26358, DNA (cytosine-5-)-methyltransferase

-
DNA chain , 2 types, 2 molecules CD

#2: DNA chain DNA (5'-D(*GP*AP*GP*GP*CP*(5CM)P*GP*CP*CP*TP*GP*C)-3')


Mass: 3678.407 Da / Num. of mol.: 1 / Source method: obtained synthetically / Source: (synth.) Homo sapiens (human)
#3: DNA chain DNA (5'-D(*GP*CP*AP*GP*G)-R(P*(PYO))-D(P*GP*GP*CP*CP*TP*C)-3')


Mass: 3665.365 Da / Num. of mol.: 1 / Source method: obtained synthetically / Source: (synth.) Homo sapiens (human)

-
Non-polymers , 4 types, 201 molecules

#4: Chemical ChemComp-ZN / ZINC ION


Mass: 65.409 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: Zn
#5: Chemical
ChemComp-EDO / 1,2-ETHANEDIOL / ETHYLENE GLYCOL / Ethylene glycol


Mass: 62.068 Da / Num. of mol.: 9 / Source method: obtained synthetically / Formula: C2H6O2
#6: Chemical ChemComp-UXM / (2R)-2-{[6-(4-aminopiperidin-1-yl)-3,5-dicyano-4-ethylpyridin-2-yl]sulfanyl}-2-phenylacetamide


Mass: 420.531 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C22H24N6OS / Feature type: SUBJECT OF INVESTIGATION
#7: Water ChemComp-HOH / water / Water


Mass: 18.015 Da / Num. of mol.: 189 / 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: 2.83 Å3/Da / Density % sol: 56.5 %
Crystal growTemperature: 292 K / Method: vapor diffusion, sitting drop / pH: 5.1
Details: 14-18% polyethylene glycol (PEG) 3350, 0.1 M citric acid (pH 5.1)

-
Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: APS / Beamline: 22-ID / Wavelength: 1 Å
DetectorType: DECTRIS EIGER X 16M / Detector: PIXEL / Date: Jun 10, 2019
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1 Å / Relative weight: 1
ReflectionResolution: 2.65→40 Å / Num. obs: 34128 / % possible obs: 98.6 % / Redundancy: 7.9 % / Biso Wilson estimate: 54.96 Å2 / Rmerge(I) obs: 0.132 / Rpim(I) all: 0.048 / Net I/σ(I): 14.8
Reflection shellResolution: 2.65→2.74 Å / Redundancy: 4 % / Rmerge(I) obs: 0.749 / Mean I/σ(I) obs: 1.7 / Num. unique obs: 3087 / CC1/2: 0.545 / CC star: 0.84 / Rpim(I) all: 0.385 / % possible all: 90.3

-
Processing

Software
NameVersionClassification
PHENIX1.17.1_3660refinement
SERGUIdata collection
HKL-2000data reduction
HKL-2000data scaling
PHENIXphasing
RefinementMethod to determine structure: FOURIER SYNTHESIS
Starting model: 6X9I

6x9i


Resolution: 2.65→40 Å / SU ML: 0.3213 / Cross valid method: FREE R-VALUE / σ(F): 1.35 / Phase error: 23.6723
Stereochemistry target values: GeoStd + Monomer Library + CDL v1.2
RfactorNum. reflection% reflection
Rfree0.2279 1706 5 %
Rwork0.1824 32408 -
obs0.1847 34114 98.44 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL
Displacement parametersBiso mean: 69.79 Å2
Refinement stepCycle: LAST / Resolution: 2.65→40 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms6511 487 68 189 7255
Refine LS restraints
Refine-IDTypeDev idealNumber
X-RAY DIFFRACTIONf_bond_d0.0047335
X-RAY DIFFRACTIONf_angle_d0.670110064
X-RAY DIFFRACTIONf_chiral_restr0.04421080
X-RAY DIFFRACTIONf_plane_restr0.00511235
X-RAY DIFFRACTIONf_dihedral_angle_d20.18692692
LS refinement shell
Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkRefine-ID% reflection obs (%)
2.65-2.730.33641260.2932411X-RAY DIFFRACTION88.18
2.73-2.820.29261380.26882603X-RAY DIFFRACTION96.18
2.82-2.920.26511430.25022711X-RAY DIFFRACTION99.24
2.92-3.030.34331420.24912710X-RAY DIFFRACTION99.76
3.03-3.170.29541430.23082724X-RAY DIFFRACTION99.79
3.17-3.340.24851450.20842727X-RAY DIFFRACTION99.72
3.34-3.550.25821430.1912725X-RAY DIFFRACTION99.58
3.55-3.820.23151430.18162713X-RAY DIFFRACTION99.37
3.82-4.20.20751440.1562741X-RAY DIFFRACTION100
4.2-4.810.17161450.13962756X-RAY DIFFRACTION100
4.81-6.060.19761460.15492773X-RAY DIFFRACTION99.9
6.06-400.19821480.16412814X-RAY DIFFRACTION99.53
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)
18.46358727559-1.366008602453.879716305083.21645574058-1.193930059795.51994969237-0.153390575862-0.274630647545-0.009764485196370.0922238818795-0.156302434318-0.7177516135560.05822391180250.4071772220560.2640687843440.6280218341740.172993857182-0.08612263544630.51247515861-0.05213897974350.5600307503194.94848782969-10.890903772129.3330731076
21.54584760795-0.7543275015740.6150576476519.525577965361.990145213754.305942567740.246450225866-0.2239419969650.2995182555030.0636140259918-0.207685634958-1.069749150910.1536187068020.652496934544-0.06371574820640.5461606731-0.142685536213-0.05917322452690.6928379782090.03277561451750.49631533074-2.7154138719120.770343230231.8368905792
34.568973243845.47624876812-1.012424343675.12438110395-1.011857227310.2269620580520.404488202873-1.265661265430.4057830361130.536806944365-0.2384640604370.112375827418-0.160213408313-0.0485517397599-0.151222432230.610665514358-0.148615870609-0.03263227490550.9879188334540.003247742977460.448407583089-30.566956904819.866721243941.2110377465
42.40814648813-0.6260544802520.0126998279130.8514297771990.176927566111.45804377067-0.00541604693204-0.1316006234890.0468774674034-0.04181725931670.1519376166840.0671231062640.0831300942534-0.0888801660218-0.1262645480450.422680340952-0.0491089205983-0.07819834403670.3109663924520.06806235537620.239301422854-34.77371735267.2087174904521.2395199758
51.18185669206-1.25192546043-1.268364237475.511211866133.805024235282.800214763220.3063710524721.82127977741-0.838552047157-0.828425250790.488278380930.7973834302860.0695072303280.811956379642-0.774351618520.94275819078-0.172546966687-0.3173736113471.222265860940.3288625364350.749556018034-46.4636360394-8.8731031566231.0164797171
68.312172965612.81042873109-2.81822980787.683327289163.628972941814.07135294589-0.9190525913770.538553271515-0.372467062922-1.095932905130.3824103707230.899026439173-0.21179443327-0.01006901582540.6805269905031.012086723270.0683169128789-0.2701041098221.063570960950.1337914514660.768133802289-45.8848357736-8.3275013790530.402416027
Refinement TLS group
IDRefine-IDRefine TLS-IDSelection details
1X-RAY DIFFRACTION1chain 'A' and (resid 730 through 878 )
2X-RAY DIFFRACTION2chain 'A' and (resid 879 through 951 )
3X-RAY DIFFRACTION3chain 'A' and (resid 952 through 1013 )
4X-RAY DIFFRACTION4chain 'A' and (resid 1014 through 1600 )
5X-RAY DIFFRACTION5chain 'C' and (resid 1 through 12 )
6X-RAY DIFFRACTION6chain 'D' and (resid 13 through 24 )

+
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