+Open data
-Basic information
Entry | Database: PDB / ID: 6w2j | ||||||
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Title | CPS1 bound to allosteric inhibitor H3B-374 | ||||||
Components | Carbamoyl-phosphate synthase [ammonia], mitochondrial | ||||||
Keywords | TRANSFERASE/TRANSFERASE INHIBITOR / inhibitor / TRANSFERASE / TRANSFERASE-TRANSFERASE INHIBITOR complex | ||||||
Function / homology | Function and homology information carbamoyl phosphate biosynthetic process / cellular response to oleic acid / monoatomic anion homeostasis / triglyceride catabolic process / modified amino acid binding / carbamoyl-phosphate synthase (ammonia) / carbamoyl-phosphate synthase (ammonia) activity / carbamoyl-phosphate synthase (glutamine-hydrolyzing) activity / midgut development / homocysteine metabolic process ...carbamoyl phosphate biosynthetic process / cellular response to oleic acid / monoatomic anion homeostasis / triglyceride catabolic process / modified amino acid binding / carbamoyl-phosphate synthase (ammonia) / carbamoyl-phosphate synthase (ammonia) activity / carbamoyl-phosphate synthase (glutamine-hydrolyzing) activity / midgut development / homocysteine metabolic process / cellular response to ammonium ion / Urea cycle / citrulline biosynthetic process / urea cycle / hepatocyte differentiation / cellular response to fibroblast growth factor stimulus / response to growth hormone / response to food / glutamate binding / nitric oxide metabolic process / response to zinc ion / glutamine metabolic process / response to dexamethasone / cellular response to glucagon stimulus / response to starvation / mitochondrial nucleoid / response to amine / small molecule binding / potassium ion binding / response to amino acid / 'de novo' pyrimidine nucleobase biosynthetic process / cellular response to cAMP / vasodilation / response to toxic substance / phospholipid binding / endopeptidase activity / response to lipopolysaccharide / mitochondrial inner membrane / mitochondrial matrix / response to xenobiotic stimulus / calcium ion binding / protein-containing complex binding / nucleolus / protein-containing complex / ATP binding / metal ion binding / plasma membrane / cytoplasm Similarity search - Function | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.62 Å | ||||||
Authors | Larsen, N.A. / Nguyen, T.V. | ||||||
Citation | Journal: Acs Med.Chem.Lett. / Year: 2020 Title: Discovery of 2,6-Dimethylpiperazines as Allosteric Inhibitors of CPS1. Authors: Rolfe, A. / Yao, S. / Nguyen, T.V. / Omoto, K. / Colombo, F. / Virrankoski, M. / Vaillancourt, F.H. / Yu, L. / Cook, A. / Reynolds, D. / Ioannidis, S. / Zhu, P. / Larsen, N.A. / Bolduc, D.M. #1: Journal: Cell Chem Biol / Year: 2020 Title: Small Molecule Inhibition of CPS1 Activity through an Allosteric Pocket. Authors: Yao, S. / Nguyen, T.V. / Rolfe, A. / Agrawal, A.A. / Ke, J. / Peng, S. / Colombo, F. / Yu, S. / Bouchard, P. / Wu, J. / Huang, K.C. / Bao, X. / Omoto, K. / Selvaraj, A. / Yu, L. / Ioannidis, ...Authors: Yao, S. / Nguyen, T.V. / Rolfe, A. / Agrawal, A.A. / Ke, J. / Peng, S. / Colombo, F. / Yu, S. / Bouchard, P. / Wu, J. / Huang, K.C. / Bao, X. / Omoto, K. / Selvaraj, A. / Yu, L. / Ioannidis, S. / Vaillancourt, F.H. / Zhu, P. / Larsen, N.A. / Bolduc, D.M. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 6w2j.cif.gz | 549.3 KB | Display | PDBx/mmCIF format |
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PDB format | pdb6w2j.ent.gz | 439.5 KB | Display | PDB format |
PDBx/mmJSON format | 6w2j.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 6w2j_validation.pdf.gz | 929.1 KB | Display | wwPDB validaton report |
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Full document | 6w2j_full_validation.pdf.gz | 951.9 KB | Display | |
Data in XML | 6w2j_validation.xml.gz | 89.6 KB | Display | |
Data in CIF | 6w2j_validation.cif.gz | 125.4 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/w2/6w2j ftp://data.pdbj.org/pub/pdb/validation_reports/w2/6w2j | HTTPS FTP |
-Related structure data
Related structure data | 6uelS S: Starting model for refinement |
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Similar structure data |
-Links
-Assembly
Deposited unit |
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1 |
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2 |
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Unit cell |
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-Components
#1: Protein | Mass: 165128.531 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: CPS1 / Production host: Spodoptera frugiperda (fall armyworm) References: UniProt: P31327, carbamoyl-phosphate synthase (ammonia) #2: Chemical | #3: Chemical | #4: Chemical | ChemComp-EDO / | #5: Water | ChemComp-HOH / | 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: 2.8 Å3/Da / Density % sol: 56.05 % |
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Crystal grow | Temperature: 293 K / Method: vapor diffusion, hanging drop Details: CPS1 protein was buffer exchanged into 50 mM glycyl-glycine pH 7.4, 50 mM KCl, 5% glycerol. CPS1 was concentrated to 10 mg/ml and H3B-4193 was added to a 5x excess molar ratio along with 1mM ...Details: CPS1 protein was buffer exchanged into 50 mM glycyl-glycine pH 7.4, 50 mM KCl, 5% glycerol. CPS1 was concentrated to 10 mg/ml and H3B-4193 was added to a 5x excess molar ratio along with 1mM AMPPNP and 1mM NAG. Ligand bound complex crystals grew by hanging drop vapor diffusion in 20% PEG 3350 and 0.2M trisodium citrate |
-Data collection
Diffraction | Mean temperature: 120 K / Serial crystal experiment: N | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Diffraction source | Source: SYNCHROTRON / Site: NSLS / Beamline: X17B1 / Wavelength: 0.9201 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Detector | Type: DECTRIS EIGER2 X 9M / Detector: PIXEL / Date: Mar 14, 2019 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Radiation wavelength | Wavelength: 0.9201 Å / Relative weight: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reflection | Resolution: 2.62→58.96 Å / Num. obs: 104121 / % possible obs: 96.6 % / Redundancy: 2.051 % / Biso Wilson estimate: 49.396 Å2 / CC1/2: 0.996 / Rmerge(I) obs: 0.072 / Rrim(I) all: 0.098 / Χ2: 0.983 / Net I/σ(I): 9.35 / Num. measured all: 213566 / Scaling rejects: 30 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reflection shell | Diffraction-ID: 1
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-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: 6UEL Resolution: 2.62→58.96 Å / Cor.coef. Fo:Fc: 0.955 / Cor.coef. Fo:Fc free: 0.921 / SU B: 15.054 / SU ML: 0.292 / Cross valid method: THROUGHOUT / σ(F): 0 / ESU R: 0.691 / ESU R Free: 0.316 Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS U VALUES : REFINED INDIVIDUALLY
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Solvent computation | Ion probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso max: 205.89 Å2 / Biso mean: 60.404 Å2 / Biso min: 20 Å2
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Refinement step | Cycle: final / Resolution: 2.62→58.96 Å
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Refine LS restraints |
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LS refinement shell | Resolution: 2.62→2.688 Å / Rfactor Rfree error: 0 / Total num. of bins used: 20
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