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Yorodumi- PDB-8fgh: Structure of human neuronal nitric oxide synthase R354A/G357D mut... -
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-Basic information
Entry | Database: PDB / ID: 8fgh | ||||||
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Title | Structure of human neuronal nitric oxide synthase R354A/G357D mutant heme domain in complex with 6-(5-(2-(dimethylamino)ethyl)-2,3-difluorophenethyl)-4-methoxypyridin-2-amine | ||||||
Components | Nitric oxide synthase, brain | ||||||
Keywords | OXIDOREDUCTASE / nitric oxide synthase inhibitor / heme enzyme | ||||||
Function / homology | Function and homology information negative regulation of calcium ion transport into cytosol / myoblast fusion / Nitric oxide stimulates guanylate cyclase / ROS and RNS production in phagocytes / negative regulation of hydrolase activity / tetrahydrobiopterin binding / arginine binding / regulation of calcium ion transmembrane transport via high voltage-gated calcium channel / retrograde trans-synaptic signaling by nitric oxide / positive regulation of sodium ion transmembrane transport ...negative regulation of calcium ion transport into cytosol / myoblast fusion / Nitric oxide stimulates guanylate cyclase / ROS and RNS production in phagocytes / negative regulation of hydrolase activity / tetrahydrobiopterin binding / arginine binding / regulation of calcium ion transmembrane transport via high voltage-gated calcium channel / retrograde trans-synaptic signaling by nitric oxide / positive regulation of sodium ion transmembrane transport / positive regulation of adenylate cyclase-activating G protein-coupled receptor signaling pathway / peptidyl-cysteine S-nitrosylation / cadmium ion binding / positive regulation of the force of heart contraction / negative regulation of potassium ion transport / negative regulation of calcium ion transport / negative regulation of serotonin uptake / sodium channel regulator activity / striated muscle contraction / nitric-oxide synthase (NADPH) / regulation of cardiac muscle contraction / multicellular organismal response to stress / xenobiotic catabolic process / nitric-oxide synthase activity / nitric oxide mediated signal transduction / arginine catabolic process / regulation of sodium ion transport / regulation of ryanodine-sensitive calcium-release channel activity / Ion homeostasis / photoreceptor inner segment / nitric oxide biosynthetic process / negative regulation of blood pressure / response to hormone / cell redox homeostasis / sarcoplasmic reticulum / muscle contraction / cell periphery / sarcolemma / cellular response to growth factor stimulus / vasodilation / calcium-dependent protein binding / FMN binding / flavin adenine dinucleotide binding / positive regulation of peptidyl-serine phosphorylation / NADP binding / response to heat / scaffold protein binding / transmembrane transporter binding / response to lipopolysaccharide / dendritic spine / postsynaptic density / response to hypoxia / cytoskeleton / calmodulin binding / membrane raft / synapse / heme binding / perinuclear region of cytoplasm / positive regulation of DNA-templated transcription / positive regulation of transcription by RNA polymerase II / protein-containing complex / mitochondrion / nucleoplasm / nucleus / plasma membrane / cytosol / cytoplasm Similarity search - Function | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / FOURIER SYNTHESIS / Resolution: 2.17 Å | ||||||
Authors | Li, H. / Poulos, T.L. | ||||||
Funding support | United States, 1items
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Citation | Journal: J.Med.Chem. / Year: 2023 Title: Potent, Selective, and Membrane Permeable 2-Amino-4-Substituted Pyridine-Based Neuronal Nitric Oxide Synthase Inhibitors. Authors: Vasu, D. / Do, H.T. / Li, H. / Hardy, C.D. / Awasthi, A. / 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 | 8fgh.cif.gz | 707.1 KB | Display | PDBx/mmCIF format |
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PDB format | pdb8fgh.ent.gz | 587.1 KB | Display | PDB format |
PDBx/mmJSON format | 8fgh.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/fg/8fgh ftp://data.pdbj.org/pub/pdb/validation_reports/fg/8fgh | HTTPS FTP |
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-Related structure data
Related structure data | 8fg9C 8fgaC 8fgbC 8fgcC 8fgdC 8fgeC 8fgfC 8fggC 8fgiC 8fgjC 8fgkC 8fglC 8fgmC 8fgnC 8fgoC 8fgpC 8fgqC 8fgrC 8fgsC 8fgtC 8fguC 8fgvC 7ts7S 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: 48996.781 Da / Num. of mol.: 4 / Mutation: R354A,G357D Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: NOS1 / Organ: brain / Plasmid: pCWori / Production host: Escherichia coli BL21(DE3) (bacteria) / References: UniProt: P29475, nitric-oxide synthase (NADPH) |
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-Non-polymers , 6 types, 626 molecules
#2: Chemical | ChemComp-HEM / #3: Chemical | ChemComp-H4B / #4: Chemical | ChemComp-XW5 / #5: Chemical | ChemComp-GOL / #6: Chemical | #7: 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: 2.74 Å3/Da / Density % sol: 55.2 % / Description: plates |
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Crystal grow | Temperature: 277 K / Method: vapor diffusion, sitting drop / pH: 7.2 Details: 8% PEG3350 35mM citric acid 65mM Bis-Tris-Propane 10% glycerol 5mM 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: 0.9794 Å | ||||||||||||||||||||||||||||||
Detector | Type: DECTRIS PILATUS 6M / Detector: PIXEL / Date: Jun 2, 2021 / Details: mirrors | ||||||||||||||||||||||||||||||
Radiation | Monochromator: DOUBLE CRYSTAL SI(III) / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray | ||||||||||||||||||||||||||||||
Radiation wavelength | Wavelength: 0.9794 Å / Relative weight: 1 | ||||||||||||||||||||||||||||||
Reflection | Resolution: 2.17→82.41 Å / Num. obs: 107704 / % possible obs: 99 % / Redundancy: 3.4 % / Biso Wilson estimate: 35.92 Å2 / CC1/2: 0.984 / Rmerge(I) obs: 0.183 / Rpim(I) all: 0.112 / Rrim(I) all: 0.216 / Net I/σ(I): 4.9 / Num. measured all: 370880 / Scaling rejects: 120 | ||||||||||||||||||||||||||||||
Reflection shell | Diffraction-ID: 1
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-Processing
Software |
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Refinement | Method to determine structure: FOURIER SYNTHESIS Starting model: 7TS7 Resolution: 2.17→61.2013 Å / SU ML: 0.32 / Cross valid method: FREE R-VALUE / σ(F): 0 / Phase error: 33.3 / 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: 180.04 Å2 / Biso mean: 57.6452 Å2 / Biso min: 17.59 Å2 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: final / Resolution: 2.17→61.2013 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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