2Y37

The discovery of novel, potent and highly selective inhibitors of inducible nitric oxide synthase (iNOS)

PDB DOI: https://doi.org/10.2210/pdb2Y37/pdb

Classification: OXIDOREDUCTASE
Organism(s): Mus musculus
Expression System: Escherichia coli BL21(DE3)
Mutation(s): No

Deposited: 2010-12-19 Released: 2011-04-13
Deposition Author(s): Cheshire, D.R., Andrews, G., Beaton, H.G., Birkinshaw, T.N., Boughton-Smith, N., Connolly, S., Cook, T.R., Cooper, A., Cooper, S.L., Cox, D., Dixon, J., Gensmantel, N., Hamley, P.J., Harrison, R., Hartopp, P., Kack, H., Luker, T., Mete, A., Millichip, I., Nicholls, D.J., Pimm, A.D., St-Gallay, S.A., Wallace, A.V.

Experimental Data Snapshot

Method: X-RAY DIFFRACTION
Resolution: 2.60 Å
R-Value Free: 0.242
R-Value Work: 0.208
R-Value Observed: 0.210

wwPDB Validation 3D Report Full Report

Ligand Structure Quality Assessment

This is version 1.4 of the entry. See complete history.

Literature

The Discovery of Novel, Potent and Highly Selective Inhibitors of Inducible Nitric Oxide Synthase (Inos).

Cheshire, D.R., Berg, A., Andersson, G.M., Andrews, G., Beaton, H.G., Birkinshaw, T.N., Boughton-Smith, N., Connolly, S., Cook, T.R., Cooper, A., Cooper, S.L., Cox, D., Dixon, J., Gensmantel, N., Hamley, P.J., Harrison, R., Hartopp, P., Kack, H., Leeson, P.D., Luker, T., Mete, A., Millichip, I., Nicholls, D.J., Pimm, A.D., St-Gallay, S.A., Wallace, A.V.

(2011) Bioorg Med Chem Lett 21: 2468

PubMed: 21398123 Search on PubMed
DOI: https://doi.org/10.1016/j.bmcl.2011.02.061
Primary Citation of Related Structures:
2Y37, 4UX6

PubMed Abstract:
By careful analysis of experimental X-ray ligand crystallographic protein data across several inhibitor series we have discovered a novel, potent and selective series of iNOS inhibitors exemplified by compound 8.

Organizational Affiliation

Department of Chemistry, AstraZeneca Charnwood, Bakewell Road, Loughborough LE11 5RH, United Kingdom. [email protected]

Macromolecule Content

Total Structure Weight: 103 kDa
Atom Count: 7,222
Modelled Residue Count: 823
Deposited Residue Count: 866
Unique protein chains: 1

Macromolecules

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Entity ID: 1
Molecule	Chains	Sequence Length	Organism	Details	Image
NITRIC OXIDE SYNTHASE, INDUCIBLE	A, B	433	Mus musculus	Mutation(s): 0 EC: 1.14.13.39
UniProt & NIH Common Fund Data Resources
Find proteins for P29477 (Mus musculus) Explore P29477 Go to UniProtKB: P29477
IMPC: MGI:97361
Entity Groups
Sequence Clusters	30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt Group	P29477
Sequence Annotations Expand
Reference Sequence

Small Molecules

Ligands 5 Unique
ID	Chains	Name / Formula / InChI Key	2D Diagram	3D Interactions
HEM Query on HEM Download Ideal Coordinates CCD File SDF format, chain G [auth A] SDF format, chain L [auth B] MOL2 format, chain G [auth A] MOL2 format, chain L [auth B] mmCIF format, chain G [auth A] mmCIF format, chain L [auth B]	G [auth A], L [auth B]	PROTOPORPHYRIN IX CONTAINING FE C₃₄ H₃₂ Fe N₄ O₄ KABFMIBPWCXCRK-RGGAHWMASA-L		Interactions Focus chain G [auth A] Focus chain L [auth B] Interactions & Density Focus chain G [auth A] Focus chain L [auth B]
A54 Query on A54 Download Ideal Coordinates CCD File SDF format, chain F [auth A] SDF format, chain K [auth B] MOL2 format, chain F [auth A] MOL2 format, chain K [auth B] mmCIF format, chain F [auth A] mmCIF format, chain K [auth B]	F [auth A], K [auth B]	2-[(1R)-3-amino-1-phenyl-propoxy]-4-chloro-benzonitrile C₁₆ H₁₅ Cl N₂ O GPCXUXJZOSOVLY-OAHLLOKOSA-N		Interactions Focus chain F [auth A] Focus chain K [auth B] Interactions & Density Focus chain F [auth A] Focus chain K [auth B]
H4B Query on H4B Download Ideal Coordinates CCD File SDF format, chain H [auth A] SDF format, chain M [auth B] MOL2 format, chain H [auth A] MOL2 format, chain M [auth B] mmCIF format, chain H [auth A] mmCIF format, chain M [auth B]	H [auth A], M [auth B]	5,6,7,8-TETRAHYDROBIOPTERIN C₉ H₁₅ N₅ O₃ FNKQXYHWGSIFBK-RPDRRWSUSA-N		Interactions Focus chain H [auth A] Focus chain M [auth B] Interactions & Density Focus chain H [auth A] Focus chain M [auth B]
SO4 Query on SO4 Download Ideal Coordinates CCD File SDF format, chain C [auth A] SDF format, chain D [auth A] SDF format, chain I [auth B] MOL2 format, chain C [auth A] MOL2 format, chain D [auth A] MOL2 format, chain I [auth B] mmCIF format, chain C [auth A] mmCIF format, chain D [auth A] mmCIF format, chain I [auth B]	C [auth A], D [auth A], I [auth B]	SULFATE ION O₄ S QAOWNCQODCNURD-UHFFFAOYSA-L		Interactions Focus chain C [auth A] Focus chain D [auth A] Focus chain I [auth B] Interactions & Density Focus chain C [auth A] Focus chain D [auth A] Focus chain I [auth B]
GOL Query on GOL Download Ideal Coordinates CCD File SDF format, chain E [auth A] SDF format, chain J [auth B] MOL2 format, chain E [auth A] MOL2 format, chain J [auth B] mmCIF format, chain E [auth A] mmCIF format, chain J [auth B]	E [auth A], J [auth B]	GLYCEROL C₃ H₈ O₃ PEDCQBHIVMGVHV-UHFFFAOYSA-N		Interactions Focus chain E [auth A] Focus chain J [auth B] Interactions & Density Focus chain E [auth A] Focus chain J [auth B]

Binding Affinity Annotations
ID	Source	Binding Affinity
A54	BindingDB: 2Y37	IC50: min: 4, max: 900 (nM) from 2 assay(s)

Experimental Data & Validation

Experimental Data

Method: X-RAY DIFFRACTION
Resolution: 2.60 Å
R-Value Free: 0.242
R-Value Work: 0.208
R-Value Observed: 0.210
Space Group: P 6₁ 2 2

Unit Cell:

Length ( Å )	Angle ( ˚ )
a = 212.492	α = 90
b = 212.492	β = 90
c = 115.372	γ = 120

Software Package:

Software Name	Purpose
BUSTER	refinement
MOSFLM	data reduction
SCALA	data scaling
PHASER	phasing

Structure Validation

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Entry History

Deposition Data

Released Date: 2011-04-13

Deposition Author(s):

Revision History (Full details and data files)

Version 1.0: 2011-04-13
Type: Initial release
Version 1.1: 2011-05-08
Changes: Version format compliance
Version 1.2: 2011-07-13
Changes: Version format compliance
Version 1.3: 2018-01-17
Changes: Data collection
Version 1.4: 2024-05-08
Changes: Data collection, Database references, Derived calculations, Other

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Help and Resources

2Y37

The discovery of novel, potent and highly selective inhibitors of inducible nitric oxide synthase (iNOS)

The Discovery of Novel, Potent and Highly Selective Inhibitors of Inducible Nitric Oxide Synthase (Inos).

Entity ID: 1

UniProt & NIH Common Fund Data Resources

Entity Groups

Sequence Annotations

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Experimental Data

Structure Validation

Ligand Structure Quality Assessment

Deposition Data

Revision History (Full details and data files)