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Yorodumi- PDB-7tsp: Structure of human endothelial nitric oxide synthase heme domain ... -
+Open data
-Basic information
Entry | Database: PDB / ID: 7tsp | ||||||
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Title | Structure of human endothelial nitric oxide synthase heme domain in complex with 6-(3-(4,4-difluoropiperidin-1-yl)prop-1-yn-1-yl)-4-methylpyridin-2-amine | ||||||
Components | Nitric oxide synthase, endothelial | ||||||
Keywords | OXIDOREDUCTASE / nitric oxide synthase inhibitor / heme enzyme | ||||||
Function / homology | Function and homology information regulation of the force of heart contraction by chemical signal / NOSIP mediated eNOS trafficking / NOSTRIN mediated eNOS trafficking / negative regulation of muscle hyperplasia / smooth muscle hyperplasia / regulation of nervous system process / ovulation from ovarian follicle / response to fluid shear stress / pulmonary valve morphogenesis / negative regulation of biomineral tissue development ...regulation of the force of heart contraction by chemical signal / NOSIP mediated eNOS trafficking / NOSTRIN mediated eNOS trafficking / negative regulation of muscle hyperplasia / smooth muscle hyperplasia / regulation of nervous system process / ovulation from ovarian follicle / response to fluid shear stress / pulmonary valve morphogenesis / negative regulation of biomineral tissue development / positive regulation of guanylate cyclase activity / Nitric oxide stimulates guanylate cyclase / regulation of systemic arterial blood pressure by endothelin / ROS and RNS production in phagocytes / tetrahydrobiopterin binding / arginine binding / aortic valve morphogenesis / endocardial cushion morphogenesis / positive regulation of Notch signaling pathway / ventricular septum morphogenesis / cadmium ion binding / negative regulation of potassium ion transport / negative regulation of calcium ion transport / actin monomer binding / negative regulation of platelet activation / blood vessel remodeling / endothelial cell migration / nitric-oxide synthase (NADPH) / positive regulation of blood vessel endothelial cell migration / nitric oxide mediated signal transduction / nitric-oxide synthase activity / negative regulation of extrinsic apoptotic signaling pathway via death domain receptors / eNOS activation / arginine catabolic process / regulation of sodium ion transport / lipopolysaccharide-mediated signaling pathway / Tetrahydrobiopterin (BH4) synthesis, recycling, salvage and regulation / homeostasis of number of cells within a tissue / nitric oxide biosynthetic process / negative regulation of blood pressure / response to hormone / removal of superoxide radicals / blood vessel diameter maintenance / cell redox homeostasis / VEGFR2 mediated vascular permeability / mitochondrion organization / establishment of localization in cell / lung development / negative regulation of smooth muscle cell proliferation / potassium ion transport / caveola / regulation of blood pressure / vasodilation / positive regulation of angiogenesis / calcium ion transport / endocytic vesicle membrane / FMN binding / flavin adenine dinucleotide binding / NADP binding / response to heat / scaffold protein binding / angiogenesis / in utero embryonic development / response to lipopolysaccharide / Extra-nuclear estrogen signaling / cytoskeleton / calmodulin binding / negative regulation of cell population proliferation / Golgi membrane / heme binding / positive regulation of gene expression / Golgi apparatus / nucleus / plasma membrane / cytosol / cytoplasm Similarity search - Function | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / FOURIER SYNTHESIS / Resolution: 2 Å | ||||||
Authors | Li, H. / Poulos, T.L. | ||||||
Funding support | United States, 1items
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Citation | Journal: Bioorg.Med.Chem. / Year: 2022 Title: 2-Aminopyridines with a shortened amino sidechain as potent, selective, and highly permeable human neuronal nitric oxide synthase inhibitors. Authors: Vasu, D. / Li, H. / Hardy, C.D. / Poulos, T.L. / Silverman, R.B. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 7tsp.cif.gz | 675.8 KB | Display | PDBx/mmCIF format |
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PDB format | pdb7tsp.ent.gz | 562 KB | Display | PDB format |
PDBx/mmJSON format | 7tsp.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 7tsp_validation.pdf.gz | 2.9 MB | Display | wwPDB validaton report |
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Full document | 7tsp_full_validation.pdf.gz | 2.9 MB | Display | |
Data in XML | 7tsp_validation.xml.gz | 69.2 KB | Display | |
Data in CIF | 7tsp_validation.cif.gz | 91.8 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/ts/7tsp ftp://data.pdbj.org/pub/pdb/validation_reports/ts/7tsp | HTTPS FTP |
-Related structure data
Related structure data | 7ts1C 7ts2C 7ts3C 7ts4C 7ts5C 7ts6C 7ts7C 7ts8C 7ts9C 7tsaC 7tsbC 7tscC 7tsdC 7tseC 7tsfC 7tsgC 7tshC 7tsiC 7tskC 7tslC 7tsmC 7tsnC 7tsoC 7uamC 7uanC 7uaoC 7us7C 7us8C 5uo8S 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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2 |
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Unit cell |
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-Components
-Protein , 1 types, 4 molecules ABCD
#1: Protein | Mass: 49345.770 Da / Num. of mol.: 4 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Cell: endothelial / Gene: NOS3 / Plasmid: pCWori / Production host: Escherichia coli BL21(DE3) (bacteria) / References: UniProt: P29474, nitric-oxide synthase (NADPH) |
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-Non-polymers , 9 types, 491 molecules
#2: Chemical | ChemComp-HEM / #3: Chemical | ChemComp-H4B / #4: Chemical | ChemComp-K8O / #5: Chemical | ChemComp-BTB / #6: Chemical | ChemComp-GOL / #7: Chemical | ChemComp-CL / #8: Chemical | ChemComp-GD / #9: Chemical | #10: Water | ChemComp-HOH / | |
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-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: 2.69 Å3/Da / Density % sol: 54.3 % / Description: rods |
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Crystal grow | Temperature: 277 K / Method: vapor diffusion, sitting drop / pH: 7.5 Details: 10-12% PEG3350, 0.1M BIS-TRIS 0.2-0.3M MG ACETATE, 0.1M GdCl3 10% glycerol, 5 mM TCEP |
-Data collection
Diffraction | Mean temperature: 100 K / Serial crystal experiment: N |
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Diffraction source | Source: SYNCHROTRON / Site: SSRL / Beamline: BL12-2 / Wavelength: 0.9795 Å |
Detector | Type: DECTRIS PILATUS 6M / Detector: PIXEL / Date: Nov 1, 2021 / Details: mirrors |
Radiation | Monochromator: DOUBLE CRYSTAL SI(III) / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 0.9795 Å / Relative weight: 1 |
Reflection | Resolution: 2→39.0198 Å / Num. obs: 128437 / % possible obs: 98.4 % / Redundancy: 4.6 % / Biso Wilson estimate: 36.07 Å2 / CC1/2: 0.994 / Rmerge(I) obs: 0.156 / Rpim(I) all: 0.081 / Rrim(I) all: 0.177 / Net I/σ(I): 5.2 |
Reflection shell | Resolution: 2→2.03 Å / Redundancy: 4.3 % / Rmerge(I) obs: 3.703 / Num. measured all: 26796 / Num. unique obs: 6232 / CC1/2: 0.344 / Rpim(I) all: 2.017 / Rrim(I) all: 4.241 / Net I/σ(I) obs: 0.5 / % possible all: 97 |
-Processing
Software |
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Refinement | Method to determine structure: FOURIER SYNTHESIS Starting model: 5UO8 Resolution: 2→39.0198 Å / SU ML: 0.31 / Cross valid method: FREE R-VALUE / σ(F): 0.64 / Phase error: 33.5 / Stereochemistry target values: ML
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Solvent computation | Shrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso max: 162.35 Å2 / Biso mean: 58.8295 Å2 / Biso min: 20.31 Å2 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: final / Resolution: 2→39.0198 Å
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Refine LS restraints |
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LS refinement shell | Refine-ID: X-RAY DIFFRACTION / Rfactor Rfree error: 0 / Total num. of bins used: 30
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Refinement TLS params. | Method: refined / Refine-ID: X-RAY DIFFRACTION
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Refinement TLS group |
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