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Yorodumi- PDB-7bht: Crystal structure of MAT2a with quinazolinone fragment 5 bound in... -
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-Basic information
Entry | Database: PDB / ID: 7bht | ||||||
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Title | Crystal structure of MAT2a with quinazolinone fragment 5 bound in the allosteric site | ||||||
Components | S-adenosylmethionine synthase isoform type-2 | ||||||
Keywords | TRANSFERASE / allosteric inhibitor / fragment-based drug design / synthetic lethal therapy / oncology | ||||||
Function / homology | Function and homology information methionine adenosyltransferase complex / methionine adenosyltransferase / methionine adenosyltransferase activity / S-adenosylmethionine biosynthetic process / Methylation / protein heterooligomerization / protein hexamerization / small molecule binding / cellular response to leukemia inhibitory factor / one-carbon metabolic process ...methionine adenosyltransferase complex / methionine adenosyltransferase / methionine adenosyltransferase activity / S-adenosylmethionine biosynthetic process / Methylation / protein heterooligomerization / protein hexamerization / small molecule binding / 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 / molecular replacement / Resolution: 1.052 Å | ||||||
Authors | Schimpl, M. / De Fusco, C. / Borjesson, U. / Cheung, T. / Collie, I. / Evans, L. / Narasimhan, P. / Stubbs, C. / Vazquez-Chantada, M. / Wagner, D.J. ...Schimpl, M. / De Fusco, C. / Borjesson, U. / Cheung, T. / Collie, I. / Evans, L. / Narasimhan, P. / Stubbs, C. / Vazquez-Chantada, M. / Wagner, D.J. / Grondine, M. / Tentarelli, S. / Underwood, E. / Argyrou, A. / Bagal, S. / Chiarparin, E. / Robb, G. / Scott, J.S. | ||||||
Citation | Journal: J.Med.Chem. / Year: 2021 Title: Fragment-Based Design of a Potent MAT2a Inhibitor and in Vivo Evaluation in an MTAP Null Xenograft Model. Authors: De Fusco, C. / Schimpl, M. / Borjesson, U. / Cheung, T. / Collie, I. / Evans, L. / Narasimhan, P. / Stubbs, C. / Vazquez-Chantada, M. / Wagner, D.J. / Grondine, M. / Sanders, M.G. / ...Authors: De Fusco, C. / Schimpl, M. / Borjesson, U. / Cheung, T. / Collie, I. / Evans, L. / Narasimhan, P. / Stubbs, C. / Vazquez-Chantada, M. / Wagner, D.J. / Grondine, M. / Sanders, M.G. / Tentarelli, S. / Underwood, E. / Argyrou, A. / Smith, J.M. / Lynch, J.T. / Chiarparin, E. / Robb, G. / Bagal, S.K. / Scott, J.S. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 7bht.cif.gz | 160.3 KB | Display | PDBx/mmCIF format |
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PDB format | pdb7bht.ent.gz | 130.5 KB | Display | PDB format |
PDBx/mmJSON format | 7bht.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/bh/7bht ftp://data.pdbj.org/pub/pdb/validation_reports/bh/7bht | HTTPS FTP |
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-Related structure data
Related structure data | 7bhrC 7bhsC 7bhuC 7bhvC 7bhwC 7bhxC C: citing same article (ref.) |
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Similar structure data |
-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: 43935.828 Da / Num. of mol.: 1 / Fragment: full length protein Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: MAT2A, AMS2, MATA2 / Plasmid: pNIC28-Bsa4 / Production host: Escherichia coli BL21(DE3) (bacteria) / Variant (production host): BL21 Gold (DE3) / References: UniProt: P31153, methionine adenosyltransferase |
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-Non-polymers , 5 types, 403 molecules
#2: Chemical | ChemComp-DMS / |
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#3: Chemical | ChemComp-TO8 / |
#4: Chemical | ChemComp-SAM / |
#5: Chemical | ChemComp-CL / |
#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: 2.12 Å3/Da / Density % sol: 42.02 % |
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Crystal grow | Temperature: 293 K / Method: vapor diffusion / pH: 8 Details: 8-12 % PEG8000, 8-12 % ethylene glycol, 0.1 M HEPES pH 8.0; soaked with 0.01 M compound (10 % DMSO) |
-Data collection
Diffraction | Mean temperature: 100 K / Serial crystal experiment: N | |||||||||||||||||||||||||||
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Diffraction source | Source: SYNCHROTRON / Site: Diamond / Beamline: I03 / Wavelength: 0.89685 Å | |||||||||||||||||||||||||||
Detector | Type: DECTRIS EIGER X 16M / Detector: PIXEL / Date: Sep 22, 2020 | |||||||||||||||||||||||||||
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray | |||||||||||||||||||||||||||
Radiation wavelength | Wavelength: 0.89685 Å / Relative weight: 1 | |||||||||||||||||||||||||||
Reflection | Resolution: 1.05→19.817 Å / Num. obs: 120837 / % possible obs: 94.9 % / Redundancy: 13.4 % / Biso Wilson estimate: 7.84 Å2 / CC1/2: 0.999 / Rmerge(I) obs: 0.105 / Rpim(I) all: 0.03 / Rrim(I) all: 0.109 / Net I/σ(I): 12.1 | |||||||||||||||||||||||||||
Reflection shell | Num. unique obs: 6042 / Diffraction-ID: 1
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-Phasing
Phasing | Method: molecular replacement |
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-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: internal model Resolution: 1.052→15.4 Å / Cor.coef. Fo:Fc: 0.968 / Cor.coef. Fo:Fc free: 0.959 / SU R Cruickshank DPI: 0.033 / Cross valid method: THROUGHOUT / σ(F): 0 / SU R Blow DPI: 0.034 / SU Rfree Blow DPI: 0.036 / SU Rfree Cruickshank DPI: 0.035
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Displacement parameters | Biso max: 63.51 Å2 / Biso mean: 13.11 Å2 / Biso min: 6.03 Å2
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Refine analyze | Luzzati coordinate error obs: 0.12 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: final / Resolution: 1.052→15.4 Å
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Refine LS restraints |
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LS refinement shell | Resolution: 1.05→1.11 Å / Rfactor Rfree error: 0 / Total num. of bins used: 50
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Refinement TLS params. | Method: refined / Origin x: 25.979 Å / Origin y: 38.7598 Å / Origin z: 32.4956 Å
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Refinement TLS group | Selection details: { A|* } |