+Open data
-Basic information
Entry | Database: PDB / ID: 4x61 | ||||||
---|---|---|---|---|---|---|---|
Title | Crystal structure of PRMT5:MEP50 with EPZ015666 and SAM | ||||||
Components |
| ||||||
Keywords | TRANSFERASE/TRANSFERASE INHIBITOR / protein-inhibitor complex / protein arginine methyltransferase / TRANSFERASE-TRANSFERASE INHIBITOR COMPLEX | ||||||
Function / homology | Function and homology information positive regulation of adenylate cyclase-inhibiting dopamine receptor signaling pathway / peptidyl-arginine N-methylation / oocyte axis specification / type II protein arginine methyltransferase / protein-arginine omega-N symmetric methyltransferase activity / peptidyl-arginine methylation / Golgi ribbon formation / negative regulation of epithelial cell proliferation involved in prostate gland development / histone H4R3 methyltransferase activity / secretory columnal luminar epithelial cell differentiation involved in prostate glandular acinus development ...positive regulation of adenylate cyclase-inhibiting dopamine receptor signaling pathway / peptidyl-arginine N-methylation / oocyte axis specification / type II protein arginine methyltransferase / protein-arginine omega-N symmetric methyltransferase activity / peptidyl-arginine methylation / Golgi ribbon formation / negative regulation of epithelial cell proliferation involved in prostate gland development / histone H4R3 methyltransferase activity / secretory columnal luminar epithelial cell differentiation involved in prostate glandular acinus development / epithelial cell proliferation involved in prostate gland development / histone arginine N-methyltransferase activity / methylosome / protein-arginine N-methyltransferase activity / methyl-CpG binding / positive regulation of mRNA splicing, via spliceosome / : / endothelial cell activation / histone H3 methyltransferase activity / Cul4B-RING E3 ubiquitin ligase complex / regulation of mitotic nuclear division / histone methyltransferase complex / positive regulation of oligodendrocyte differentiation / histone methyltransferase activity / E-box binding / negative regulation of cell differentiation / ubiquitin-like ligase-substrate adaptor activity / spliceosomal snRNP assembly / ribonucleoprotein complex binding / regulation of ERK1 and ERK2 cascade / nuclear receptor coactivator activity / regulation of signal transduction by p53 class mediator / methyltransferase activity / liver regeneration / DNA-templated transcription termination / circadian regulation of gene expression / Regulation of TP53 Activity through Methylation / RMTs methylate histone arginines / protein polyubiquitination / transcription corepressor activity / p53 binding / snRNP Assembly / ubiquitin-dependent protein catabolic process / chromatin remodeling / protein heterodimerization activity / positive regulation of cell population proliferation / chromatin / regulation of DNA-templated transcription / regulation of transcription by RNA polymerase II / Golgi apparatus / nucleoplasm / identical protein binding / nucleus / cytosol / cytoplasm Similarity search - Function | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.85 Å | ||||||
Authors | Boriack-Sjodin, P.A. | ||||||
Citation | Journal: Nat.Chem.Biol. / Year: 2015 Title: A selective inhibitor of PRMT5 with in vivo and in vitro potency in MCL models. Authors: Chan-Penebre, E. / Kuplast, K.G. / Majer, C.R. / Boriack-Sjodin, P.A. / Wigle, T.J. / Johnston, L.D. / Rioux, N. / Munchhof, M.J. / Jin, L. / Jacques, S.L. / West, K.A. / Lingaraj, T. / ...Authors: Chan-Penebre, E. / Kuplast, K.G. / Majer, C.R. / Boriack-Sjodin, P.A. / Wigle, T.J. / Johnston, L.D. / Rioux, N. / Munchhof, M.J. / Jin, L. / Jacques, S.L. / West, K.A. / Lingaraj, T. / Stickland, K. / Ribich, S.A. / Raimondi, A. / Scott, M.P. / Waters, N.J. / Pollock, R.M. / Smith, J.J. / Barbash, O. / Pappalardi, M. / Ho, T.F. / Nurse, K. / Oza, K.P. / Gallagher, K.T. / Kruger, R. / Moyer, M.P. / Copeland, R.A. / Chesworth, R. / Duncan, K.W. | ||||||
History |
|
-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
---|
-Downloads & links
-Download
PDBx/mmCIF format | 4x61.cif.gz | 203.2 KB | Display | PDBx/mmCIF format |
---|---|---|---|---|
PDB format | pdb4x61.ent.gz | 156.8 KB | Display | PDB format |
PDBx/mmJSON format | 4x61.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/x6/4x61 ftp://data.pdbj.org/pub/pdb/validation_reports/x6/4x61 | HTTPS FTP |
---|
-Related structure data
-Links
-Assembly
Deposited unit |
| ||||||||
---|---|---|---|---|---|---|---|---|---|
1 |
| ||||||||
Unit cell |
|
-Components
-Protein , 2 types, 2 molecules AB
#1: Protein | Mass: 73763.625 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Details: coexpressed with MEP50 / Source: (gene. exp.) Homo sapiens (human) / Gene: PRMT5, HRMT1L5, IBP72, JBP1, SKB1 / Cell line (production host): Sf9 / Production host: Spodoptera frugiperda (fall armyworm) References: UniProt: O14744, Transferases; Transferring one-carbon groups; Methyltransferases, EC: 2.1.1.125 |
---|---|
#2: Protein | Mass: 37862.406 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Details: coexpressed with PRMT5 / Source: (gene. exp.) Homo sapiens (human) / Gene: WDR77, MEP50, WD45, HKMT1069, Nbla10071 / Cell line (production host): Sf9 / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: Q9BQA1 |
-Non-polymers , 4 types, 61 molecules
#3: Chemical | ChemComp-SAM / |
---|---|
#4: Chemical | ChemComp-3XV / |
#5: Chemical | ChemComp-GOL / |
#6: Water | ChemComp-HOH / |
-Experimental details
-Experiment
Experiment | Method: X-RAY DIFFRACTION / Number of used crystals: 1 |
---|
-Sample preparation
Crystal | Density Matthews: 3.01 Å3/Da / Density % sol: 59.08 % |
---|---|
Crystal grow | Temperature: 293 K / Method: vapor diffusion, hanging drop / pH: 6.1 Details: 0.2 M Sodium acetate, 0.1 M Sodium citrate pH 6.1, 10% w/v PEG 4000 |
-Data collection
Diffraction | Mean temperature: 100 K | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Diffraction source | Source: SYNCHROTRON / Site: APS / Beamline: 22-ID / Wavelength: 1 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Detector | Type: MARMOSAIC 300 mm CCD / Detector: CCD / Date: Feb 12, 2014 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Radiation wavelength | Wavelength: 1 Å / Relative weight: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reflection | Resolution: 2.85→50 Å / Num. obs: 28661 / % possible obs: 96.5 % / Redundancy: 5.9 % / Rmerge(I) obs: 0.117 / Χ2: 1.015 / Net I/av σ(I): 13.75 / Net I/σ(I): 7.2 / Num. measured all: 170361 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reflection shell | Diffraction-ID: 1 / Rejects: 0
|
-Processing
Software |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Refinement | Method to determine structure: MOLECULAR REPLACEMENT / Resolution: 2.85→50 Å / Cor.coef. Fo:Fc: 0.938 / Cor.coef. Fo:Fc free: 0.894 / SU B: 18.746 / SU ML: 0.338 / Cross valid method: THROUGHOUT / σ(F): 0 / ESU R Free: 0.402 / Stereochemistry target values: MAXIMUM LIKELIHOOD Details: HYDROGENS HAVE BEEN USED IF PRESENT IN THE INPUT U VALUES : REFINED INDIVIDUALLY
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Solvent computation | Ion probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å / Solvent model: MASK | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso max: 135.91 Å2 / Biso mean: 65.5 Å2 / Biso min: 22.61 Å2
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: final / Resolution: 2.85→50 Å
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refine LS restraints |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
LS refinement shell | Resolution: 2.855→2.929 Å / Total num. of bins used: 20
|