2XHD

Crystal structure of N-((2S)-5-(6-fluoro-3-pyridinyl)-2,3-dihydro-1H- inden-2-yl)-2-propanesulfonamide in complex with the ligand binding domain of the human GluA2 receptor

PDB DOI: https://doi.org/10.2210/pdb2XHD/pdb

Classification: TRANSPORT PROTEIN
Organism(s): Homo sapiens
Expression System: Escherichia coli BL21(DE3)
Mutation(s): Yes

Deposited: 2010-06-14 Released: 2010-07-21
Deposition Author(s): Ward, S.E., Harries, M., Aldegheri, L., Andreotti, D., Ballantine, S., Bax, B.D., Harris, A.J., Harker, A.J., Lund, J., Melarange, R., Mingardi, A., Mookherjee, C., Mosley, J., Neve, M., Oliosi, B., Profeta, R., Smith, K.J., Smith, P.W., Spada, S., Thewlis, K.M., Yusaf, S.P.

Experimental Data Snapshot

Method: X-RAY DIFFRACTION
Resolution: 1.80 Å
R-Value Free: 0.238
R-Value Work: 0.200
R-Value Observed: 0.202

wwPDB Validation 3D Report Full Report

Ligand Structure Quality Assessment

This is version 1.3 of the entry. See complete history.

Literature

Discovery of N-[(2S)-5-(6-Fluoro-3-Pyridinyl)-2,3-Dihydro-1H-Inden-2-Yl]-2-Propanesulfonamide, a Novel Clinical Ampa Receptor Positive Modulator.

Ward, S.E., Harries, M., Aldegheri, L., Andreotti, D., Ballantine, S., Bax, B.D., Harris, A.J., Harker, A.J., Lund, J., Melarange, R., Mingardi, A., Mookherjee, C., Mosley, J., Neve, M., Oliosi, B., Profeta, R., Smith, K.J., Smith, P.W., Spada, S., Thewlis, K.M., Yusaf, S.P.

(2010) J Med Chem 53: 5801

PubMed: 20614889 Search on PubMed
DOI: https://doi.org/10.1021/jm1005429
Primary Citation of Related Structures:
2XHD

PubMed Abstract:
A series of AMPA receptor positive allosteric modulators has been optimized from poorly penetrant leads to identify molecules with excellent preclinical pharmacokinetics and CNS penetration. These discoveries led to 17i, a potent, efficacious CNS penetrant molecule with an excellent pharmacokinetic profile across preclinical species, which is well tolerated and is also orally bioavailable in humans.

Organizational Affiliation

Neurosciences Centre of Excellence for Drug Discovery, GlaxoSmithKline, New Frontiers Science Park, Harlow, Essex, UK. [email protected]

Macromolecule Content

Total Structure Weight: 59.66 kDa
Atom Count: 4,834
Modelled Residue Count: 517
Deposited Residue Count: 526
Unique protein chains: 1

Macromolecules

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(by identity cutoff) | 3D Structure

Entity ID: 1
Molecule	Chains	Sequence Length	Organism	Details	Image
GLUTAMATE RECEPTOR 2	A, B	263	Homo sapiens	Mutation(s): 1
UniProt & NIH Common Fund Data Resources
Find proteins for P42262 (Homo sapiens) Explore P42262 Go to UniProtKB: P42262
PHAROS: P42262 GTEx: ENSG00000120251
Entity Groups
Sequence Clusters	30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt Group	P42262
Sequence Annotations Expand
Reference Sequence

Small Molecules

Ligands 3 Unique
ID	Chains	Name / Formula / InChI Key	2D Diagram	3D Interactions
7T9 Query on 7T9 Download Ideal Coordinates CCD File SDF format, chain G [auth B] MOL2 format, chain G [auth B] mmCIF format, chain G [auth B]	G [auth B]	N-[(2S)-5-(6-FLUORO-3-PYRIDINYL)-2,3-DIHYDRO-1H-INDEN-2-YL]-2-PROPANESULFONAMIDE C₁₇ H₁₉ F N₂ O₂ S QXQSUBKWSHMXDP-INIZCTEOSA-N		Interactions Focus chain G [auth B] Interactions & Density Focus chain G [auth B]
GLU Query on GLU Download Ideal Coordinates CCD File SDF format, chain C [auth A] SDF format, chain F [auth B] MOL2 format, chain C [auth A] MOL2 format, chain F [auth B] mmCIF format, chain C [auth A] mmCIF format, chain F [auth B]	C [auth A], F [auth B]	GLUTAMIC ACID C₅ H₉ N O₄ WHUUTDBJXJRKMK-VKHMYHEASA-N		Interactions Focus chain C [auth A] Focus chain F [auth B] Interactions & Density Focus chain C [auth A] Focus chain F [auth B]
SO4 Query on SO4 Download Ideal Coordinates CCD File SDF format, chain D [auth A] SDF format, chain E [auth A] SDF format, chain H [auth B] SDF format, chain I [auth B] SDF format, chain J [auth B] MOL2 format, chain D [auth A] MOL2 format, chain E [auth A] MOL2 format, chain H [auth B] MOL2 format, chain I [auth B] MOL2 format, chain J [auth B] mmCIF format, chain D [auth A] mmCIF format, chain E [auth A] mmCIF format, chain H [auth B] mmCIF format, chain I [auth B] mmCIF format, chain J [auth B]	D [auth A], E [auth A], H [auth B], I [auth B], J [auth B]	SULFATE ION O₄ S QAOWNCQODCNURD-UHFFFAOYSA-L		Interactions Focus chain D [auth A] Focus chain E [auth A] Focus chain H [auth B] Focus chain I [auth B] Focus chain J [auth B] Interactions & Density Focus chain D [auth A] Focus chain E [auth A] Focus chain H [auth B] Focus chain I [auth B] Focus chain J [auth B]

Experimental Data & Validation

Experimental Data

Method: X-RAY DIFFRACTION
Resolution: 1.80 Å
R-Value Free: 0.238
R-Value Work: 0.200
R-Value Observed: 0.202
Space Group: P 2₁ 2₁ 2

Unit Cell:

Length ( Å )	Angle ( ˚ )
a = 99.139	α = 90
b = 121.781	β = 90
c = 47.49	γ = 90

Software Package:

Software Name	Purpose
REFMAC	refinement
HKL	data reduction
SCALEPACK	data scaling

Structure Validation

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Ligand Structure Quality Assessment

Entry History

Deposition Data

Released Date: 2010-07-21

Deposition Author(s):

Revision History (Full details and data files)

Version 1.0: 2010-07-21
Type: Initial release
Version 1.1: 2011-05-26
Changes: Version format compliance
Version 1.2: 2011-07-13
Changes: Version format compliance
Version 1.3: 2024-11-20
Changes: Data collection, Database references, Derived calculations, Other, Structure summary

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Help and Resources

2XHD

Crystal structure of N-((2S)-5-(6-fluoro-3-pyridinyl)-2,3-dihydro-1H- inden-2-yl)-2-propanesulfonamide in complex with the ligand binding domain of the human GluA2 receptor

Discovery of N-[(2S)-5-(6-Fluoro-3-Pyridinyl)-2,3-Dihydro-1H-Inden-2-Yl]-2-Propanesulfonamide, a Novel Clinical Ampa Receptor Positive Modulator.

Entity ID: 1

UniProt & NIH Common Fund Data Resources

Entity Groups

Sequence Annotations

Expand

Experimental Data

Structure Validation

Ligand Structure Quality Assessment

Deposition Data

Revision History (Full details and data files)