+Open data
-Basic information
Entry | Database: PDB / ID: 6x9i | ||||||
---|---|---|---|---|---|---|---|
Title | Human DNMT1(729-1600) Bound to Zebularine-Containing 12mer dsDNA | ||||||
Components |
| ||||||
Keywords | TRANSFERASE / EPIGENETICS / DNA METHYLTRANSFERASE FOLD / MAINTENANCE METHYLATION | ||||||
Function / homology | Function and homology information chromosomal DNA methylation maintenance following DNA replication / negative regulation of vascular associated smooth muscle cell differentiation involved in phenotypic switching / epigenetic programming of gene expression / cellular response to bisphenol A / DNA-methyltransferase activity / negative regulation of vascular associated smooth muscle cell apoptotic process / DNA (cytosine-5-)-methyltransferase / DNA (cytosine-5-)-methyltransferase activity / SUMOylation of DNA methylation proteins / DNA methylation-dependent heterochromatin formation ...chromosomal DNA methylation maintenance following DNA replication / negative regulation of vascular associated smooth muscle cell differentiation involved in phenotypic switching / epigenetic programming of gene expression / cellular response to bisphenol A / DNA-methyltransferase activity / negative regulation of vascular associated smooth muscle cell apoptotic process / DNA (cytosine-5-)-methyltransferase / DNA (cytosine-5-)-methyltransferase activity / SUMOylation of DNA methylation proteins / DNA methylation-dependent heterochromatin formation / STAT3 nuclear events downstream of ALK signaling / female germ cell nucleus / methyl-CpG binding / negative regulation of gene expression via chromosomal CpG island methylation / Nuclear events stimulated by ALK signaling in cancer / pericentric heterochromatin / positive regulation of vascular associated smooth muscle cell proliferation / DNA methylation / PRC2 methylates histones and DNA / replication fork / Defective pyroptosis / promoter-specific chromatin binding / cellular response to amino acid stimulus / NoRC negatively regulates rRNA expression / methylation / 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 | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.2 Å | ||||||
Authors | Pathuri, S. / Horton, J.R. / Cheng, X. | ||||||
Funding support | United States, 1items
| ||||||
Citation | Journal: 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 |
|
-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
---|
-Downloads & links
-Download
PDBx/mmCIF format | 6x9i.cif.gz | 418.7 KB | Display | PDBx/mmCIF format |
---|---|---|---|---|
PDB format | pdb6x9i.ent.gz | 295.1 KB | Display | PDB format |
PDBx/mmJSON format | 6x9i.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 6x9i_validation.pdf.gz | 486.7 KB | Display | wwPDB validaton report |
---|---|---|---|---|
Full document | 6x9i_full_validation.pdf.gz | 496.2 KB | Display | |
Data in XML | 6x9i_validation.xml.gz | 32.6 KB | Display | |
Data in CIF | 6x9i_validation.cif.gz | 46.3 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/x9/6x9i ftp://data.pdbj.org/pub/pdb/validation_reports/x9/6x9i | HTTPS FTP |
-Related structure data
Related structure data | 6x9jC 6x9kC 3swrS S: Starting model for refinement C: citing same article (ref.) |
---|---|
Similar structure data |
-Links
-Assembly
Deposited unit |
| ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
1 |
| ||||||||||||
Unit cell |
| ||||||||||||
Components on special symmetry positions |
|
-Components
-Protein , 1 types, 1 molecules A
#1: Protein | 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(DE3) (bacteria) / Strain (production host): BL21(DE3) / Variant (production host): Gold References: UniProt: P26358, DNA (cytosine-5-)-methyltransferase |
---|
-DNA chain , 2 types, 2 molecules CD
#2: DNA chain | Mass: 3678.407 Da / Num. of mol.: 1 / Source method: obtained synthetically / Source: (synth.) Homo sapiens (human) |
---|---|
#3: DNA chain | Mass: 3665.365 Da / Num. of mol.: 1 / Source method: obtained synthetically / Source: (synth.) Homo sapiens (human) |
-Non-polymers , 5 types, 233 molecules
#4: Chemical | ChemComp-SAH / | ||||||
---|---|---|---|---|---|---|---|
#5: Chemical | #6: Chemical | ChemComp-EDO / #7: Chemical | ChemComp-GOL / | #8: Water | ChemComp-HOH / | |
-Details
Has ligand of interest | N |
---|
-Experimental details
-Experiment
Experiment | Method: X-RAY DIFFRACTION / Number of used crystals: 1 |
---|
-Sample preparation
Crystal | Density Matthews: 2.96 Å3/Da / Density % sol: 58.43 % |
---|---|
Crystal grow | Temperature: 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
Diffraction | Mean temperature: 100 K / Serial crystal experiment: N |
---|---|
Diffraction source | Source: SYNCHROTRON / Site: APS / Beamline: 22-ID / Wavelength: 1 Å |
Detector | Type: DECTRIS EIGER X 16M / Detector: PIXEL / Date: Oct 28, 2018 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 1 Å / Relative weight: 1 |
Reflection | Resolution: 2.2→45.21 Å / Num. obs: 55268 / % possible obs: 95.3 % / Redundancy: 4.3 % / Biso Wilson estimate: 45.6 Å2 / Rmerge(I) obs: 0.159 / Rpim(I) all: 0.076 / Net I/σ(I): 9.4 |
Reflection shell | Resolution: 2.2→2.33 Å / Rmerge(I) obs: 1.021 / Mean I/σ(I) obs: 1.6 / Num. unique obs: 4682 / CC1/2: 0.453 / CC star: 0.789 / Rpim(I) all: 0.662 / % possible all: 81.5 |
-Processing
Software |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: 3SWR Resolution: 2.2→45.21 Å / SU ML: 0.2583 / Cross valid method: FREE R-VALUE / σ(F): 1.33 / Phase error: 27.2122 Stereochemistry target values: GeoStd + Monomer Library + CDL v1.2
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Solvent computation | Shrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso mean: 70.81 Å2 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: LAST / Resolution: 2.2→45.21 Å
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refine LS restraints |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
LS refinement shell |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement TLS params. | Method: refined / Refine-ID: X-RAY DIFFRACTION
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement TLS group |
|