+Open data
-Basic information
Entry | Database: PDB / ID: 9eyw | ||||||
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Title | Human PRMT5 in complex with AZ compound 21 | ||||||
Components |
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Keywords | TRANSFERASE / methyl transferase / inhibitor | ||||||
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 / histone arginine N-methyltransferase activity / epithelial cell proliferation involved in prostate gland development / protein-arginine N-methyltransferase activity / methylosome / E-box binding / methyl-CpG binding / endothelial cell activation / histone H3 methyltransferase activity / positive regulation of mRNA splicing, via spliceosome / negative regulation of gene expression via chromosomal CpG island methylation / regulation of mitotic nuclear division / Cul4B-RING E3 ubiquitin ligase complex / histone methyltransferase complex / positive regulation of oligodendrocyte differentiation / histone methyltransferase activity / negative regulation of cell differentiation / ubiquitin-like ligase-substrate adaptor activity / ribonucleoprotein complex binding / regulation of ERK1 and ERK2 cascade / spliceosomal snRNP assembly / liver regeneration / nuclear receptor coactivator activity / regulation of signal transduction by p53 class mediator / methyltransferase activity / DNA-templated transcription termination / circadian regulation of gene expression / Regulation of TP53 Activity through Methylation / p53 binding / RMTs methylate histone arginines / protein polyubiquitination / transcription corepressor activity / snRNP Assembly / ubiquitin-dependent protein catabolic process / chromatin remodeling / protein heterodimerization activity / positive regulation of cell population proliferation / regulation of transcription by RNA polymerase II / chromatin / regulation of DNA-templated transcription / Golgi apparatus / nucleoplasm / identical protein binding / nucleus / cytoplasm / cytosol Similarity search - Function | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.3 Å | ||||||
Authors | Debreczeni, J. | ||||||
Funding support | 1items
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Citation | Journal: J.Med.Chem. / Year: 2024 Title: Discovery and In Vivo Efficacy of AZ-PRMT5i-1, a Novel PRMT5 Inhibitor with High MTA Cooperativity. Authors: Smith, J.M. / Barlaam, B. / Beattie, D. / Bradshaw, L. / Chan, H.M. / Chiarparin, E. / Collingwood, O. / Cooke, S.L. / Cronin, A. / Cumming, I. / Dean, E. / Debreczeni, J.E. / Del Barco ...Authors: Smith, J.M. / Barlaam, B. / Beattie, D. / Bradshaw, L. / Chan, H.M. / Chiarparin, E. / Collingwood, O. / Cooke, S.L. / Cronin, A. / Cumming, I. / Dean, E. / Debreczeni, J.E. / Del Barco Barrantes, I. / Diene, C. / Gianni, D. / Guerot, C. / Guo, X. / Guven, S. / Hayhow, T.G. / Hong, T. / Kemmitt, P.D. / Lamont, G.M. / Lamont, S. / Lynch, J.T. / McWilliams, L. / Moore, S. / Raubo, P. / Robb, G.R. / Robinson, J. / Scott, J.S. / Srinivasan, B. / Steward, O. / Stubbs, C.J. / Syson, K. / Tan, L. / Turner, O. / Underwood, E. / Urosevic, J. / Vazquez-Chantada, M. / Whittaker, A.L. / Wilson, D.M. / Winter-Holt, J.J. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 9eyw.cif.gz | 381.2 KB | Display | PDBx/mmCIF format |
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PDB format | pdb9eyw.ent.gz | Display | PDB format | |
PDBx/mmJSON format | 9eyw.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 9eyw_validation.pdf.gz | 417 KB | Display | wwPDB validaton report |
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Full document | 9eyw_full_validation.pdf.gz | 417 KB | Display | |
Data in XML | 9eyw_validation.xml.gz | 1.3 KB | Display | |
Data in CIF | 9eyw_validation.cif.gz | 10.3 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/ey/9eyw ftp://data.pdbj.org/pub/pdb/validation_reports/ey/9eyw | HTTPS FTP |
-Related structure data
Related structure data | 9eyuC 9eyvC 9eyxC C: citing same article (ref.) |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
-Assembly
Deposited unit |
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1 |
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Unit cell |
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-Components
-Protein , 2 types, 2 molecules AB
#1: Protein | Mass: 72766.664 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: PRMT5, HRMT1L5, IBP72, JBP1, SKB1 / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: O14744 |
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#2: Protein | Mass: 36757.246 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: WDR77, MEP50, WD45, HKMT1069, Nbla10071 / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: Q9BQA1 |
-Non-polymers , 4 types, 64 molecules
#3: Chemical | ChemComp-A1H8B / ( Mass: 473.474 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C26H21F2N5O2 / Feature type: SUBJECT OF INVESTIGATION |
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#4: Chemical | ChemComp-MTA / |
#5: Chemical | ChemComp-SO4 / |
#6: Water | ChemComp-HOH / |
-Details
Has ligand of interest | Y |
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-Experimental details
-Experiment
Experiment | Method: X-RAY DIFFRACTION / Number of used crystals: 1 |
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-Sample preparation
Crystal | Density Matthews: 2.87 Å3/Da / Density % sol: 57.14 % |
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Crystal grow | Temperature: 293 K / Method: vapor diffusion, sitting drop Details: 14-16 w/v % PEG3350, 24-25 v/v % 2-methyl-2,4-pentanediol and 0.1 M tri-sodium-citrate buffer at pH 5.4 |
-Data collection
Diffraction | Mean temperature: 100 K / Serial crystal experiment: N |
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Diffraction source | Source: SYNCHROTRON / Site: Diamond / Beamline: I04 / Wavelength: 0.95373 Å |
Detector | Type: DECTRIS EIGER2 XE 16M / Detector: PIXEL / Date: Jan 24, 2023 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 0.95373 Å / Relative weight: 1 |
Reflection | Resolution: 2.171→109.961 Å / Num. obs: 30125 / % possible obs: 92.9 % / Redundancy: 6.9 % / CC1/2: 0.998 / Net I/σ(I): 9 |
Reflection shell | Resolution: 2.171→2.482 Å / Num. unique obs: 1506 / CC1/2: 0.777 |
-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT / Resolution: 2.3→10 Å / Cor.coef. Fo:Fc: 0.872 / Cor.coef. Fo:Fc free: 0.863 / SU B: 27.931 / SU ML: 0.319 / Cross valid method: THROUGHOUT / ESU R Free: 0.448 / Stereochemistry target values: MAXIMUM LIKELIHOOD / Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS
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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 mean: 62.527 Å2
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Refinement step | Cycle: 1 / Resolution: 2.3→10 Å
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