[English] 日本語
Yorodumi
- PDB-3e7t: Structure of murine iNOS oxygenase domain with inhibitor AR-C102222 -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 3e7t
TitleStructure of murine iNOS oxygenase domain with inhibitor AR-C102222
ComponentsNitric oxide synthase, inducible
KeywordsOXIDOREDUCTASE / NITRIC OXIDE SYNTHASE / NOS / HEME / TETRAHYDROBIOPTERIN / OXIDOREDUCTASE Calmodulin-binding / FAD / FMN / Iron / Metal-binding / NADP / Polymorphism / Zinc
Function / homology
Function and homology information


Nitric oxide stimulates guanylate cyclase / ROS and RNS production in phagocytes / G protein-coupled receptor signaling pathway coupled to cGMP nucleotide second messenger / Peroxisomal protein import / cAMP-dependent protein kinase regulator activity / prostaglandin secretion / positive regulation of killing of cells of another organism / tetrahydrobiopterin binding / arginine binding / cortical cytoskeleton ...Nitric oxide stimulates guanylate cyclase / ROS and RNS production in phagocytes / G protein-coupled receptor signaling pathway coupled to cGMP nucleotide second messenger / Peroxisomal protein import / cAMP-dependent protein kinase regulator activity / prostaglandin secretion / positive regulation of killing of cells of another organism / tetrahydrobiopterin binding / arginine binding / cortical cytoskeleton / superoxide metabolic process / cGMP-mediated signaling / nitric-oxide synthase binding / peptidyl-cysteine S-nitrosylation / regulation of cytokine production involved in inflammatory response / cellular response to cytokine stimulus / regulation of insulin secretion / cellular response to organic cyclic compound / nitric-oxide synthase (NADPH) / blood vessel remodeling / nitric oxide mediated signal transduction / response to tumor necrosis factor / nitric-oxide synthase activity / arginine catabolic process / nitric oxide biosynthetic process / negative regulation of blood pressure / response to hormone / positive regulation of interleukin-8 production / response to bacterium / Hsp90 protein binding / negative regulation of protein catabolic process / beta-catenin binding / regulation of blood pressure / cellular response to type II interferon / circadian rhythm / positive regulation of interleukin-6 production / peroxisome / cellular response to xenobiotic stimulus / FMN binding / NADP binding / actin binding / regulation of cell population proliferation / flavin adenine dinucleotide binding / cellular response to lipopolysaccharide / response to lipopolysaccharide / calmodulin binding / response to hypoxia / intracellular signal transduction / defense response to bacterium / cadherin binding / inflammatory response / positive regulation of apoptotic process / negative regulation of gene expression / heme binding / protein kinase binding / perinuclear region of cytoplasm / protein homodimerization activity / extracellular space / identical protein binding / nucleus / metal ion binding / plasma membrane / cytosol / cytoplasm
Similarity search - Function
Bovine Endothelial Nitric Oxide Synthase Heme Domain; Chain: A,domain 3 / Nitric Oxide Synthase; Chain A, domain 3 / Nitric Oxide Synthase; Chain A, domain 1 / Nitric Oxide Synthase; Chain A, domain 1 / Nitric Oxide Synthase;Heme Domain; Chain A, domain 2 / Nitric Oxide Synthase;Heme Domain;Chain A domain 2 / Nitric-oxide synthase, eukaryote / Nitric oxide synthase, domain 2 superfamily / Nitric oxide synthase, domain 1 superfamily / Nitric oxide synthase, domain 3 superfamily ...Bovine Endothelial Nitric Oxide Synthase Heme Domain; Chain: A,domain 3 / Nitric Oxide Synthase; Chain A, domain 3 / Nitric Oxide Synthase; Chain A, domain 1 / Nitric Oxide Synthase; Chain A, domain 1 / Nitric Oxide Synthase;Heme Domain; Chain A, domain 2 / Nitric Oxide Synthase;Heme Domain;Chain A domain 2 / Nitric-oxide synthase, eukaryote / Nitric oxide synthase, domain 2 superfamily / Nitric oxide synthase, domain 1 superfamily / Nitric oxide synthase, domain 3 superfamily / Nitric oxide synthase, N-terminal / Nitric oxide synthase, N-terminal domain superfamily / Nitric oxide synthase, oxygenase domain / Nitric oxide synthase (NOS) signature. / Sulfite reductase [NADPH] flavoprotein alpha-component-like, FAD-binding / NADPH-cytochrome p450 reductase, FAD-binding, alpha-helical domain superfamily / FAD binding domain / Flavodoxin-like / Flavoprotein pyridine nucleotide cytochrome reductase / Flavodoxin / Flavodoxin-like domain profile. / Flavodoxin/nitric oxide synthase / Oxidoreductase FAD/NAD(P)-binding / Oxidoreductase NAD-binding domain / FAD-binding domain, ferredoxin reductase-type / Ferredoxin-NADP reductase (FNR), nucleotide-binding domain / Ferredoxin reductase-type FAD binding domain profile. / Riboflavin synthase-like beta-barrel / Flavoprotein-like superfamily / Alpha-Beta Complex / Alpha Beta
Similarity search - Domain/homology
Chem-B14 / 7,8-DIHYDROBIOPTERIN / PROTOPORPHYRIN IX CONTAINING FE / Nitric oxide synthase, inducible
Similarity search - Component
Biological speciesMus musculus (house mouse)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.6 Å
AuthorsGarcin, E.D. / Arvai, A.S. / Rosenfeld, R.J. / Kroeger, M.D. / Crane, B.R. / Andersson, G. / Andrews, G. / Hamley, P.J. / Mallinder, P.R. / Nicholls, D.J. ...Garcin, E.D. / Arvai, A.S. / Rosenfeld, R.J. / Kroeger, M.D. / Crane, B.R. / Andersson, G. / Andrews, G. / Hamley, P.J. / Mallinder, P.R. / Nicholls, D.J. / St-Gallay, S.A. / Tinker, A.C. / Gensmantel, N.P. / Mete, A. / Cheshire, D.R. / Connolly, S. / Stuehr, D.J. / Aberg, A. / Wallace, A.V. / Tainer, J.A. / Getzoff, E.D.
CitationJournal: Nat.Chem.Biol. / Year: 2008
Title: Anchored plasticity opens doors for selective inhibitor design in nitric oxide synthase.
Authors: Garcin, E.D. / Arvai, A.S. / Rosenfeld, R.J. / Kroeger, M.D. / Crane, B.R. / Andersson, G. / Andrews, G. / Hamley, P.J. / Mallinder, P.R. / Nicholls, D.J. / St-Gallay, S.A. / Tinker, A.C. / ...Authors: Garcin, E.D. / Arvai, A.S. / Rosenfeld, R.J. / Kroeger, M.D. / Crane, B.R. / Andersson, G. / Andrews, G. / Hamley, P.J. / Mallinder, P.R. / Nicholls, D.J. / St-Gallay, S.A. / Tinker, A.C. / Gensmantel, N.P. / Mete, A. / Cheshire, D.R. / Connolly, S. / Stuehr, D.J. / Aberg, A. / Wallace, A.V. / Tainer, J.A. / Getzoff, E.D.
History
DepositionAug 18, 2008Deposition site: RCSB / Processing site: RCSB
Revision 1.0Oct 7, 2008Provider: repository / Type: Initial release
Revision 1.1Jul 13, 2011Group: Version format compliance
Revision 2.0Feb 21, 2024Group: Atomic model / Data collection ...Atomic model / Data collection / Database references / Derived calculations
Category: atom_site / chem_comp_atom ...atom_site / chem_comp_atom / chem_comp_bond / database_2 / struct_site
Item: _atom_site.occupancy / _database_2.pdbx_DOI ..._atom_site.occupancy / _database_2.pdbx_DOI / _database_2.pdbx_database_accession / _struct_site.pdbx_auth_asym_id / _struct_site.pdbx_auth_comp_id / _struct_site.pdbx_auth_seq_id

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Nitric oxide synthase, inducible
B: Nitric oxide synthase, inducible
hetero molecules


Theoretical massNumber of molelcules
Total (without water)102,8149
Polymers100,2422
Non-polymers2,5727
Water5,837324
1
A: Nitric oxide synthase, inducible
hetero molecules

A: Nitric oxide synthase, inducible
hetero molecules


Theoretical massNumber of molelcules
Total (without water)102,91010
Polymers100,2422
Non-polymers2,6688
Water362
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
crystal symmetry operation11_655-x+y+1,y,-z+1/21
Buried area12170 Å2
ΔGint-104 kcal/mol
Surface area33650 Å2
MethodPISA
2
B: Nitric oxide synthase, inducible
hetero molecules

B: Nitric oxide synthase, inducible
hetero molecules


Theoretical massNumber of molelcules
Total (without water)102,7188
Polymers100,2422
Non-polymers2,4766
Water362
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
crystal symmetry operation9_766-x+2,-x+y+1,-z+5/31
Buried area11730 Å2
ΔGint-70 kcal/mol
Surface area33560 Å2
MethodPISA
Unit cell
Length a, b, c (Å)214.156, 214.156, 116.950
Angle α, β, γ (deg.)90.000, 90.000, 120.000
Int Tables number178
Space group name H-MP6122

-
Components

-
Protein , 1 types, 2 molecules AB

#1: Protein Nitric oxide synthase, inducible / E.C.1.14.13.39 / NOS TYPE II / INDUCIBLE NOS / INOS / MACROPHAGE NOS / MAC-NOS


Mass: 50120.953 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Mus musculus (house mouse) / Gene: Nos2, Inosl / Plasmid: PCWORI / Production host: Escherichia coli (E. coli) / Strain (production host): BL21(DE3) / References: UniProt: P29477, nitric-oxide synthase (NADPH)

-
Non-polymers , 5 types, 331 molecules

#2: Chemical ChemComp-SO4 / SULFATE ION


Mass: 96.063 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: SO4
#3: Chemical ChemComp-HEM / PROTOPORPHYRIN IX CONTAINING FE / HEME


Mass: 616.487 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C34H32FeN4O4
#4: Chemical ChemComp-HBI / 7,8-DIHYDROBIOPTERIN


Mass: 239.231 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C9H13N5O3
#5: Chemical ChemComp-B14 / 1-(6-CYANO-3-PYRIDYLCARBONYL)-5',8'-DIFLUOROSPIRO[PIPERIDINE-4,2'(1'H)-QUINAZOLINE]-4'-AMINE / AR-C102222


Mass: 382.367 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C19H16F2N6O
#6: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 324 / Source method: isolated from a natural source / Formula: H2O

-
Experimental details

-
Experiment

ExperimentMethod: X-RAY DIFFRACTION / Number of used crystals: 1

-
Sample preparation

CrystalDensity Matthews: 3.86 Å3/Da / Density % sol: 68.15 %
Crystal growTemperature: 298 K / Method: vapor diffusion, hanging drop / pH: 6
Details: LITHIUM SULFATE, MES, BOG, PH 6.0, VAPOR DIFFUSION, HANGING DROP, TEMPERATURE 298K

-
Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: SYNCHROTRON / Site: SSRL / Beamline: BL7-1 / Wavelength: 1.08
DetectorType: ADSC QUANTUM 4 / Detector: CCD / Date: Feb 16, 1998
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1.08 Å / Relative weight: 1
ReflectionResolution: 2.6→20 Å / Num. obs: 44360 / % possible obs: 96.2 % / Observed criterion σ(I): 0 / Biso Wilson estimate: 42.3 Å2 / Rmerge(I) obs: 0.064 / Rsym value: 0.064
Reflection shellResolution: 2.6→2.69 Å / Rmerge(I) obs: 0.407 / Mean I/σ(I) obs: 2.7 / Rsym value: 0.407 / % possible all: 93.6

-
Processing

Software
NameVersionClassificationNB
CNSrefinement
PDB_EXTRACT3.006data extraction
DENZOdata reduction
SCALEPACKdata scaling
CNSphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT / Resolution: 2.6→19.99 Å / Occupancy max: 1 / Occupancy min: 1 / Data cutoff high absF: 415130 / Data cutoff low absF: 0 / Isotropic thermal model: RESTRAINED / Cross valid method: THROUGHOUT / σ(F): 0 / Stereochemistry target values: ENGH & HUBER
RfactorNum. reflection% reflectionSelection details
Rfree0.263 2231 -RANDOM
Rwork0.232 ---
obs-44360 90.6 %-
Solvent computationSolvent model: FLAT MODEL / Bsol: 47.03 Å2 / ksol: 0.31 e/Å3
Displacement parametersBiso max: 144.45 Å2 / Biso mean: 52.166 Å2 / Biso min: 18.53 Å2
Baniso -1Baniso -2Baniso -3
1--10.61 Å2-1.36 Å20 Å2
2---10.61 Å20 Å2
3---21.23 Å2
Refinement stepCycle: LAST / Resolution: 2.6→19.99 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms6736 0 181 324 7241
Refine LS restraints
Refine-IDTypeDev ideal
X-RAY DIFFRACTIONc_bond_d0.008
X-RAY DIFFRACTIONc_angle_deg1.3
X-RAY DIFFRACTIONc_dihedral_angle_d22.3
X-RAY DIFFRACTIONc_improper_angle_d0.95
X-RAY DIFFRACTIONc_mcbond_it
X-RAY DIFFRACTIONc_mcangle_it
X-RAY DIFFRACTIONc_scbond_it
X-RAY DIFFRACTIONc_scangle_it
LS refinement shellResolution: 2.6→2.69 Å / Num. reflection Rwork: 6568 / Total num. of bins used: 6
Xplor file
Refine-IDSerial noParam fileTopol file
X-RAY DIFFRACTION1PROTEIN_REP.TOPPROTEIN_REP.PARAM
X-RAY DIFFRACTION2WATER.TOPWATER.PARAM
X-RAY DIFFRACTION3ION.TOPION.PARAM
X-RAY DIFFRACTION4TOPH19X.HEMEPARAM19X.HEME
X-RAY DIFFRACTION5B14.TOPB14.PAR
X-RAY DIFFRACTION6

+
About Yorodumi

-
News

-
Feb 9, 2022. New format data for meta-information of EMDB entries

New format data for meta-information of EMDB entries

  • Version 3 of the EMDB header file is now the official format.
  • The previous official version 1.9 will be removed from the archive.

Related info.:EMDB header

External links:wwPDB to switch to version 3 of the EMDB data model

-
Aug 12, 2020. Covid-19 info

Covid-19 info

URL: https://pdbjlvh1.pdbj.org/emnavi/covid19.php

New page: Covid-19 featured information page in EM Navigator.

Related info.:Covid-19 info / Mar 5, 2020. Novel coronavirus structure data

+
Mar 5, 2020. Novel coronavirus structure data

Novel coronavirus structure data

Related info.:Yorodumi Speices / Aug 12, 2020. Covid-19 info

External links:COVID-19 featured content - PDBj / Molecule of the Month (242)：Coronavirus Proteases

+
Jan 31, 2019. EMDB accession codes are about to change! (news from PDBe EMDB page)

EMDB accession codes are about to change! (news from PDBe EMDB page)

  • The allocation of 4 digits for EMDB accession codes will soon come to an end. Whilst these codes will remain in use, new EMDB accession codes will include an additional digit and will expand incrementally as the available range of codes is exhausted. The current 4-digit format prefixed with “EMD-” (i.e. EMD-XXXX) will advance to a 5-digit format (i.e. EMD-XXXXX), and so on. It is currently estimated that the 4-digit codes will be depleted around Spring 2019, at which point the 5-digit format will come into force.
  • The EM Navigator/Yorodumi systems omit the EMD- prefix.

Related info.:Q: What is EMD? / ID/Accession-code notation in Yorodumi/EM Navigator

External links:EMDB Accession Codes are Changing Soon! / Contact to PDBj

+
Jul 12, 2017. Major update of PDB

Major update of PDB

  • wwPDB released updated PDB data conforming to the new PDBx/mmCIF dictionary.
  • This is a major update changing the version number from 4 to 5, and with Remediation, in which all the entries are updated.
  • In this update, many items about electron microscopy experimental information are reorganized (e.g. em_software).
  • Now, EM Navigator and Yorodumi are based on the updated data.

External links:wwPDB Remediation / Enriched Model Files Conforming to OneDep Data Standards Now Available in the PDB FTP Archive

-
Yorodumi

Thousand views of thousand structures

  • Yorodumi is a browser for structure data from EMDB, PDB, SASBDB, etc.
  • This page is also the successor to EM Navigator detail page, and also detail information page/front-end page for Omokage search.
  • The word "yorodu" (or yorozu) is an old Japanese word meaning "ten thousand". "mi" (miru) is to see.

Related info.:EMDB / PDB / SASBDB / Comparison of 3 databanks / Yorodumi Search / Aug 31, 2016. New EM Navigator & Yorodumi / Yorodumi Papers / Jmol/JSmol / Function and homology information / Changes in new EM Navigator and Yorodumi

Read more