[English] 日本語
Yorodumi
- PDB-3nw2: Novel nanomolar Imidazopyridines as selective Nitric Oxide Syntha... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 3nw2
TitleNovel nanomolar Imidazopyridines as selective Nitric Oxide Synthase (iNOS) inhibitors: SAR and structural insights
ComponentsNitric oxide synthase, inducible
KeywordsOXIDOREDUCTASE/OXIDOREDUCTASE inhibitor / CALMODULIN-BINDING / FAD / FMN / IRON / METAL-BINDING / NADP / OXIDOREDUCTASE-OXIDOREDUCTASE inhibitor complex
Function / homology
Function and homology information


Nitric oxide stimulates guanylate cyclase / ROS and RNS production in phagocytes / Peroxisomal protein import / positive regulation of killing of cells of another organism / prostaglandin secretion / tetrahydrobiopterin binding / arginine binding / peptidyl-cysteine S-nitrosylation / cortical cytoskeleton / superoxide metabolic process ...Nitric oxide stimulates guanylate cyclase / ROS and RNS production in phagocytes / Peroxisomal protein import / positive regulation of killing of cells of another organism / prostaglandin secretion / tetrahydrobiopterin binding / arginine binding / peptidyl-cysteine S-nitrosylation / cortical cytoskeleton / superoxide metabolic process / cellular response to cytokine stimulus / regulation of cytokine production involved in inflammatory response / : / nitric-oxide synthase (NADPH) / nitric-oxide synthase activity / arginine catabolic process / nitric oxide biosynthetic process / regulation of insulin secretion / positive regulation of interleukin-8 production / response to bacterium / negative regulation of protein catabolic process / cellular response to type II interferon / positive regulation of interleukin-6 production / circadian rhythm / cellular response to xenobiotic stimulus / FMN binding / peroxisome / NADP binding / flavin adenine dinucleotide binding / regulation of cell population proliferation / cellular response to lipopolysaccharide / response to lipopolysaccharide / response to hypoxia / calmodulin binding / defense response to bacterium / inflammatory response / negative regulation of gene expression / heme binding / perinuclear region of cytoplasm / protein homodimerization activity / metal ion binding / 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, N-terminal / Nitric oxide synthase, N-terminal domain superfamily / Nitric oxide synthase, domain 2 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, N-terminal / Nitric oxide synthase, N-terminal domain superfamily / Nitric oxide synthase, domain 2 superfamily / Nitric oxide synthase, domain 1 superfamily / Nitric oxide synthase, domain 3 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
5,6,7,8-TETRAHYDROBIOPTERIN / PROTOPORPHYRIN IX CONTAINING FE / Chem-MPW / Nitric oxide synthase, inducible
Similarity search - Component
Biological speciesMus musculus (house mouse)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.8 Å
AuthorsGraedler, U. / Fuchss, T. / Ulrich, W.R. / Boer, R. / Strub, A. / Hesslinger, C. / Anezo, C. / Diederichs, K. / Zaliani, A.
CitationJournal: Bioorg.Med.Chem.Lett. / Year: 2011
Title: Novel nanomolar imidazo[4,5-b]pyridines as selective nitric oxide synthase (iNOS) inhibitors: SAR and structural insights
Authors: Graedler, U. / Fuchss, T. / Ulrich, W.R. / Boer, R. / Strub, A. / Hesslinger, C. / Anezo, C. / Diederichs, K. / Zaliani, A.
History
DepositionJul 9, 2010Deposition site: RCSB / Processing site: PDBJ
Revision 1.0Jun 22, 2011Provider: repository / Type: Initial release
Revision 1.1Jul 13, 2011Group: Version format compliance
Revision 1.2Dec 21, 2011Group: Database references
Revision 1.3Nov 8, 2017Group: Refinement description / Category: software
Revision 1.4Nov 1, 2023Group: Data collection / Database references ...Data collection / Database references / Derived calculations / Refinement description
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / database_2 / diffrn_source / pdbx_initial_refinement_model / struct_site
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession ..._database_2.pdbx_DOI / _database_2.pdbx_database_accession / _diffrn_source.pdbx_synchrotron_site / _struct_site.pdbx_auth_asym_id / _struct_site.pdbx_auth_comp_id / _struct_site.pdbx_auth_seq_id
Revision 1.5Oct 30, 2024Group: Structure summary / Category: pdbx_entry_details / pdbx_modification_feature

-
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)100,3179
Polymers97,9972
Non-polymers2,3207
Water1,51384
1
A: Nitric oxide synthase, inducible
hetero molecules

A: Nitric oxide synthase, inducible
hetero molecules


Theoretical massNumber of molelcules
Total (without water)100,41410
Polymers97,9972
Non-polymers2,4168
Water362
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
crystal symmetry operation11_655-x+y+1,y,-z+1/21
Buried area6570 Å2
ΔGint-41 kcal/mol
Surface area35680 Å2
MethodPISA
2
B: Nitric oxide synthase, inducible
hetero molecules

B: Nitric oxide synthase, inducible
hetero molecules


Theoretical massNumber of molelcules
Total (without water)100,2218
Polymers97,9972
Non-polymers2,2246
Water362
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
crystal symmetry operation9_766-x+2,-x+y+1,-z+5/31
Buried area6360 Å2
ΔGint-37 kcal/mol
Surface area35240 Å2
MethodPISA
Unit cell
Length a, b, c (Å)212.600, 212.600, 111.500
Angle α, β, γ (deg.)90.00, 90.00, 120.00
Int Tables number178
Space group name H-MP6122

-
Components

-
Protein , 1 types, 2 molecules AB

#1: Protein Nitric oxide synthase, inducible / Inducible NO synthase / Inducible NOS / iNOS / NOS type II / Macrophage NOS / MAC-NOS


Mass: 48998.691 Da / Num. of mol.: 2 / Fragment: RESIDUES 77-499
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Mus musculus (house mouse) / Production host: Escherichia coli (E. coli) / References: UniProt: P29477, nitric-oxide synthase (NADPH)

-
Non-polymers , 5 types, 91 molecules

#2: Chemical ChemComp-HEM / PROTOPORPHYRIN IX CONTAINING FE / HEME


Mass: 616.487 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C34H32FeN4O4
#3: Chemical ChemComp-H4B / 5,6,7,8-TETRAHYDROBIOPTERIN


Mass: 241.247 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C9H15N5O3 / Comment: neurotransmitter*YM
#4: Chemical ChemComp-SO4 / SULFATE ION


Mass: 96.063 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: SO4
#5: Chemical ChemComp-MPW / 2-[2-(4-methoxypyridin-2-yl)ethyl]-3H-imidazo[4,5-b]pyridine


Mass: 254.287 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C14H14N4O
#6: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 84 / Source method: isolated from a natural source / Formula: H2O

-
Details

Has protein modificationY

-
Experimental details

-
Experiment

ExperimentMethod: X-RAY DIFFRACTION / Number of used crystals: 2

-
Sample preparation

CrystalDensity Matthews: 3.71 Å3/Da / Density % sol: 66.86 %
Crystal growTemperature: 291 K / Method: vapor diffusion, hanging drop / pH: 6
Details: 1M ammonium sulfate, 33.3mM Mes buffer pH 6.0, 6.7mM DTT, 6.7mM BH4, 5% beta-octyl glycoside, VAPOR DIFFUSION, HANGING DROP, temperature 291K

-
Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: SYNCHROTRON / Site: EMBL/DESY, HAMBURG / Beamline: X13 / Wavelength: 0.8017 Å
DetectorType: MAR CCD 130 mm / Detector: CCD / Date: Aug 1, 2001
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.8017 Å / Relative weight: 1
ReflectionResolution: 2.8→50 Å / Num. obs: 36767 / % possible obs: 99.4 % / Observed criterion σ(I): 0 / Redundancy: 9.38 % / Rmerge(I) obs: 0.216 / Net I/σ(I): 8.22 / Num. measured all: 345021
Reflection shellResolution: 2.8→2.9 Å / Redundancy: 9.26 % / Rmerge(I) obs: 1.306 / Mean I/σ(I) obs: 1.25 / % possible all: 99.9

-
Processing

Software
NameClassification
CNSrefinement
XDSdata reduction
XSCALEdata scaling
CNSphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: PDB ENTRY 1NOD

1nod


Resolution: 2.8→19.72 Å / Occupancy max: 1 / Occupancy min: 1 / Cross valid method: THROUGHOUT / σ(F): 0 / Stereochemistry target values: Engh & Huber
RfactorNum. reflection% reflectionSelection details
Rfree0.3234 1824 4.9 %RANDOM
Rwork0.2794 34941 --
all-36967 --
obs-36765 99.5 %-
Solvent computationBsol: 39.1985 Å2
Displacement parametersBiso max: 168.12 Å2 / Biso mean: 77.6278 Å2 / Biso min: 1 Å2
Baniso -1Baniso -2Baniso -3
1-23.199 Å2-1.88 Å20 Å2
2--23.199 Å20 Å2
3----46.397 Å2
Refinement stepCycle: LAST / Resolution: 2.8→19.72 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms6744 0 163 84 6991
Refine LS restraints
Refine-IDTypeDev idealDev ideal target
X-RAY DIFFRACTIONc_mcbond_it6.1016
X-RAY DIFFRACTIONc_scbond_it9.028
X-RAY DIFFRACTIONc_mcangle_it9.0288
X-RAY DIFFRACTIONc_scangle_it12.22910

+
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://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