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Yorodumi- PDB-8xar: Structure-Based Design and Optimization of Methionine Adenosyltra... -
+Open data
-Basic information
Entry | Database: PDB / ID: 8xar | ||||||
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Title | Structure-Based Design and Optimization of Methionine Adenosyltransferase 2A (MAT2A) Inhibitors with SAM and Compound 54 | ||||||
Components | S-adenosylmethionine synthase isoform type-2 | ||||||
Keywords | TRANSFERASE / One-carbon metabolism / Metal-binding / inhibitor complex | ||||||
Function / homology | Function and homology information methionine adenosyltransferase complex / methionine adenosyltransferase / methionine adenosyltransferase activity / cellular response to methionine / Methylation / S-adenosylmethionine biosynthetic process / protein heterooligomerization / protein hexamerization / small molecule binding / positive regulation of TORC1 signaling ...methionine adenosyltransferase complex / methionine adenosyltransferase / methionine adenosyltransferase activity / cellular response to methionine / Methylation / S-adenosylmethionine biosynthetic process / protein heterooligomerization / protein hexamerization / small molecule binding / positive regulation of TORC1 signaling / cellular response to leukemia inhibitory factor / one-carbon metabolic process / ATP binding / identical protein binding / metal ion binding / cytosol Similarity search - Function | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.19 Å | ||||||
Authors | Zheng, J.Y. / Zhang, G.P. / Li, J.J. / Tong, S.L. | ||||||
Funding support | China, 1items
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Citation | Journal: J.Med.Chem. / Year: 2024 Title: Structure-Based Design and Optimization of Methionine Adenosyltransferase 2A (MAT2A) Inhibitors with High Selectivity, Brain Penetration, and In Vivo Efficacy. Authors: Zheng, J. / Zhang, T. / Tong, S. / Liu, T. / Cui, J. / Xu, H. / Hu, D. / Shen, Y. / Yin, Y. / Zhao, D. / Tan, C. / Dong, X. / Chen, J. / Ji, F. / Tong, C. / Li, J.J. / Li, J. / Zhang, G. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 8xar.cif.gz | 200.3 KB | Display | PDBx/mmCIF format |
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PDB format | pdb8xar.ent.gz | 154.2 KB | Display | PDB format |
PDBx/mmJSON format | 8xar.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 8xar_validation.pdf.gz | 1 MB | Display | wwPDB validaton report |
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Full document | 8xar_full_validation.pdf.gz | 1 MB | Display | |
Data in XML | 8xar_validation.xml.gz | 22.1 KB | Display | |
Data in CIF | 8xar_validation.cif.gz | 34.6 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/xa/8xar ftp://data.pdbj.org/pub/pdb/validation_reports/xa/8xar | HTTPS FTP |
-Related structure data
Related structure data | 8xb0C 7bhrS S: Starting model for refinement 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 on special symmetry positions |
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-Components
-Protein , 1 types, 1 molecules A
#1: Protein | Mass: 45562.617 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: MAT2A / Production host: Escherichia coli BL21(DE3) (bacteria) / References: UniProt: P31153, methionine adenosyltransferase |
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-Non-polymers , 6 types, 540 molecules
#2: Chemical | ChemComp-YMW / Mass: 324.764 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C17H13ClN4O / Feature type: SUBJECT OF INVESTIGATION | ||||
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#3: Chemical | ChemComp-GOL / | ||||
#4: Chemical | ChemComp-SAM / | ||||
#5: Chemical | #6: Chemical | ChemComp-CL / | #7: 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: 2.06 Å3/Da / Density % sol: 40.42 % |
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Crystal grow | Temperature: 291 K / Method: vapor diffusion, hanging drop Details: 0.1M Tris pH 8.0; 0.2M LiCl; 10% EG; 18%-22% PEG6000 |
-Data collection
Diffraction | Mean temperature: 100 K / Serial crystal experiment: N |
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Diffraction source | Source: SYNCHROTRON / Site: APS / Beamline: 19-ID / Wavelength: 0.97935 Å |
Detector | Type: DECTRIS PILATUS3 X 6M / Detector: PIXEL / Date: Apr 2, 2022 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 0.97935 Å / Relative weight: 1 |
Reflection | Resolution: 1.19→47.12 Å / Num. obs: 117262 / % possible obs: 97.6 % / Redundancy: 13.2 % / CC1/2: 0.999 / Rmerge(I) obs: 0.078 / Rpim(I) all: 0.022 / Rrim(I) all: 0.081 / Χ2: 0.99 / Net I/σ(I): 18.2 |
Reflection shell | Resolution: 1.19→1.21 Å / % possible obs: 89.3 % / Redundancy: 12.4 % / Rmerge(I) obs: 1.317 / Num. measured all: 65936 / Num. unique obs: 5304 / CC1/2: 0.799 / Rpim(I) all: 0.379 / Rrim(I) all: 1.371 / Χ2: 0.93 / Net I/σ(I) obs: 2.3 |
-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: 7BHR Resolution: 1.19→47.12 Å / Cor.coef. Fo:Fc: 0.987 / Cor.coef. Fo:Fc free: 0.984 / SU B: 1.462 / SU ML: 0.027 / Cross valid method: THROUGHOUT / ESU R: 0.03 / ESU R Free: 0.03 / 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: 11.948 Å2
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Refinement step | Cycle: 1 / Resolution: 1.19→47.12 Å
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Refine LS restraints |
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