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Yorodumi- PDB-6av2: Structure of human neuronal nitric oxide synthase R354A/G357D mut... -
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-Basic information
Entry | Database: PDB / ID: 6av2 | ||||||
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Title | Structure of human neuronal nitric oxide synthase R354A/G357D mutant heme domain in complex with 6-(3-(3-(dimethylamino)propyl)-5-(trifluoromethyl)phenethyl)-4-methylpyridin-2-amine | ||||||
Components | Nitric oxide synthase, brain | ||||||
Keywords | OXIDOREDUCTASE / nitric oxide synthase inhibitor complex heme enzyme | ||||||
Function / homology | Function and homology information positive regulation of membrane repolarization during ventricular cardiac muscle cell action potential / negative regulation of calcium ion transport into cytosol / Nitric oxide stimulates guanylate cyclase / myoblast fusion / ROS and RNS production in phagocytes / negative regulation of hydrolase activity / tetrahydrobiopterin binding / arginine binding / regulation of cardiac muscle contraction by calcium ion signaling / regulation of calcium ion transmembrane transport via high voltage-gated calcium channel ...positive regulation of membrane repolarization during ventricular cardiac muscle cell action potential / negative regulation of calcium ion transport into cytosol / Nitric oxide stimulates guanylate cyclase / myoblast fusion / ROS and RNS production in phagocytes / negative regulation of hydrolase activity / tetrahydrobiopterin binding / arginine binding / regulation of cardiac muscle contraction by calcium ion signaling / 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 / calcium channel regulator activity / sodium channel regulator activity / nitric-oxide synthase (NADPH) / regulation of cardiac muscle contraction / multicellular organismal response to stress / nitric-oxide synthase activity / xenobiotic catabolic process / arginine catabolic process / striated muscle contraction / regulation of sodium ion transport / nitric oxide mediated signal transduction / Ion homeostasis / regulation of ryanodine-sensitive calcium-release channel activity / nitric oxide biosynthetic process / negative regulation of blood pressure / photoreceptor inner segment / cell redox homeostasis / sarcoplasmic reticulum / response to hormone / muscle contraction / cell periphery / sarcolemma / cellular response to growth factor stimulus / vasodilation / calcium-dependent protein binding / FMN binding / positive regulation of peptidyl-serine phosphorylation / NADP binding / flavin adenine dinucleotide binding / response to heat / scaffold protein binding / transmembrane transporter binding / response to lipopolysaccharide / dendritic spine / postsynaptic density / cytoskeleton / calmodulin binding / response to hypoxia / 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: 2.1 Å | ||||||
Authors | Li, H. / Poulos, T.L. | ||||||
Funding support | United States, 1items
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Citation | Journal: J. Med. Chem. / Year: 2017 Title: Improvement of Cell Permeability of Human Neuronal Nitric Oxide Synthase Inhibitors Using Potent and Selective 2-Aminopyridine-Based Scaffolds with a Fluorobenzene Linker. Authors: Do, H.T. / Wang, H.Y. / Li, H. / Chreifi, G. / 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 | 6av2.cif.gz | 363.2 KB | Display | PDBx/mmCIF format |
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PDB format | pdb6av2.ent.gz | 295.9 KB | Display | PDB format |
PDBx/mmJSON format | 6av2.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/av/6av2 ftp://data.pdbj.org/pub/pdb/validation_reports/av/6av2 | HTTPS FTP |
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-Related structure data
Related structure data | 6auqC 6aurC 6ausC 6autC 6auuC 6auvC 6auwC 6auxC 6auyC 6auzC 6av0C 6av1C 6av3C 6av4C 6av5C 6av6C 6av7C 4uh5S C: citing same article (ref.) 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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Unit cell |
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-Components
-Protein , 1 types, 2 molecules AB
#1: Protein | Mass: 48784.496 Da / Num. of mol.: 2 / Fragment: UNP residues 302-722 / Mutation: R354A,G357D Source method: isolated from a genetically manipulated source Details: Residues 344 to 351 are disordered / Source: (gene. exp.) Homo sapiens (human) / Gene: NOS1 / Organ: brain / Plasmid: pCWori / Production host: ESCHERICHIA COLI (E. coli) / Strain (production host): BL21(DE3) / References: UniProt: P29475, nitric-oxide synthase (NADPH) |
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-Non-polymers , 5 types, 414 molecules
#2: Chemical | #3: Chemical | #4: Chemical | #5: Chemical | ChemComp-ZN / | #6: Water | ChemComp-HOH / | |
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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: 55.4 % / Description: plate |
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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 |
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Diffraction source | Source: SYNCHROTRON / Site: ALS / Beamline: 8.2.1 / Wavelength: 1 Å |
Detector | Type: ADSC QUANTUM 315 / Detector: CCD / Date: Oct 24, 2015 / Details: mirrors |
Radiation | Monochromator: graphite / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 1 Å / Relative weight: 1 |
Reflection | Resolution: 2.1→51 Å / Num. obs: 60809 / % possible obs: 97.9 % / Observed criterion σ(I): -3 / Redundancy: 5.4 % / CC1/2: 0.991 / Rmerge(I) obs: 0.148 / Rsym value: 0.148 / Net I/σ(I): 6.5 |
Reflection shell | Resolution: 2.1→2.18 Å / Redundancy: 5.4 % / Rmerge(I) obs: 1.689 / Mean I/σ(I) obs: 0.8 / Num. unique obs: 4365 / CC1/2: 0.416 / % possible all: 96.9 |
-Processing
Software |
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Refinement | Method to determine structure: FOURIER SYNTHESIS Starting model: 4UH5 Resolution: 2.1→50.173 Å / SU ML: 0.28 / Cross valid method: FREE R-VALUE / σ(F): 0.26 / Phase error: 26.08
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Solvent computation | Shrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: LAST / Resolution: 2.1→50.173 Å
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Refine LS restraints |
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LS refinement shell |
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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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