3ZPQ

Thermostabilised turkey beta1 adrenergic receptor with 4-(piperazin-1- yl)-1H-indole bound (compound 19)

PDB DOI: https://doi.org/10.2210/pdb3ZPQ/pdb

Classification: MEMBRANE PROTEIN
Organism(s): Meleagris gallopavo
Expression System: Trichoplusia ni
Mutation(s): Yes
Membrane Protein: Yes PDBTMMemProtMD

Deposited: 2013-03-01 Released: 2013-04-03
Deposition Author(s): Christopher, J.A., Congreve, M., Dore, A.S., Marshall, F.H., Myszka, D.G., Brown, J., Koglin, M., Tehan, B., Errey, J.C., Tate, C.G., Warne, T.

Experimental Data Snapshot

Method: X-RAY DIFFRACTION
Resolution: 2.80 Å
R-Value Free: 0.274
R-Value Work: 0.220
R-Value Observed: 0.223

Starting Model: experimental
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Ligand Structure Quality Assessment

This is version 1.5 of the entry. See complete history.

Literature

Biophysical Fragment Screening of the Beta1-Adrenergic Receptor: Identification of High Affinity Aryl Piperazine Leads Using Structure-Based Drug Design.

Christopher, J., Brown, J., Dore, A., Errey, J., Koglin, M., Marshall, F.H., Myszka, D., Rich, R.L., Tate, C.G., Tehan, B., Warne, T., Congreve, M.

(2013) J Med Chem 56: 3446

PubMed: 23517028 Search on PubMedSearch on PubMed Central
DOI: https://doi.org/10.1021/jm400140q
Primary Citation of Related Structures:
3ZPQ, 3ZPR

PubMed Abstract:
Biophysical fragment screening of a thermostabilized β1-adrenergic receptor (β1AR) using surface plasmon resonance (SPR) enabled the identification of moderate affinity, high ligand efficiency (LE) arylpiperazine hits 7 and 8. Subsequent hit to lead follow-up confirmed the activity of the chemotype, and a structure-based design approach using protein-ligand crystal structures of the β1AR resulted in the identification of several fragments that bound with higher affinity, including indole 19 and quinoline 20. In the first example of GPCR crystallography with ligands derived from fragment screening, structures of the stabilized β1AR complexed with 19 and 20 were determined at resolutions of 2.8 and 2.7 Å, respectively.

Organizational Affiliation

Heptares Therapeutics Ltd. , BioPark, Welwyn Garden City, Hertfordshire, AL7 3AX, U.K. [email protected]

Macromolecule Content

Total Structure Weight: 77.72 kDa
Atom Count: 4,996
Modelled Residue Count: 586
Deposited Residue Count: 630
Unique protein chains: 1

Macromolecules

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(by identity cutoff) | 3D Structure

Entity ID: 1
Molecule	Chains	Sequence Length	Organism	Details	Image
BETA-1 ADRENERGIC RECEPTOR	A, B	315	Meleagris gallopavo	Mutation(s): 8 Membrane Entity: Yes
UniProt
Find proteins for P07700 (Meleagris gallopavo) Explore P07700 Go to UniProtKB: P07700
Entity Groups
Sequence Clusters	30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt Group	P07700
Sequence Annotations Expand
Reference Sequence

Small Molecules

Ligands 4 Unique
ID	Chains	Name / Formula / InChI Key	2D Diagram	3D Interactions
Y01 Query on Y01 Download Ideal Coordinates CCD File SDF format, chain C [auth A] SDF format, chain D [auth A] SDF format, chain K [auth B] SDF format, chain L [auth B] MOL2 format, chain C [auth A] MOL2 format, chain D [auth A] MOL2 format, chain K [auth B] MOL2 format, chain L [auth B] mmCIF format, chain C [auth A] mmCIF format, chain D [auth A] mmCIF format, chain K [auth B] mmCIF format, chain L [auth B]	C [auth A], D [auth A], K [auth B], L [auth B]	CHOLESTEROL HEMISUCCINATE C₃₁ H₅₀ O₄ WLNARFZDISHUGS-MIXBDBMTSA-N		Interactions Focus chain C [auth A] Focus chain D [auth A] Focus chain K [auth B] Focus chain L [auth B] Interactions & Density Focus chain C [auth A] Focus chain D [auth A] Focus chain K [auth B] Focus chain L [auth B]
2CV Query on 2CV Download Ideal Coordinates CCD File SDF format, chain E [auth A] SDF format, chain F [auth A] SDF format, chain G [auth A] SDF format, chain H [auth A] SDF format, chain M [auth B] SDF format, chain N [auth B] SDF format, chain O [auth B] SDF format, chain P [auth B] SDF format, chain Q [auth B] MOL2 format, chain E [auth A] MOL2 format, chain F [auth A] MOL2 format, chain G [auth A] MOL2 format, chain H [auth A] MOL2 format, chain M [auth B] MOL2 format, chain N [auth B] MOL2 format, chain O [auth B] MOL2 format, chain P [auth B] MOL2 format, chain Q [auth B] mmCIF format, chain E [auth A] mmCIF format, chain F [auth A] mmCIF format, chain G [auth A] mmCIF format, chain H [auth A] mmCIF format, chain M [auth B] mmCIF format, chain N [auth B] mmCIF format, chain O [auth B] mmCIF format, chain P [auth B] mmCIF format, chain Q [auth B]	E [auth A] F [auth A] G [auth A] H [auth A] M [auth B] E [auth A], F [auth A], G [auth A], H [auth A], M [auth B], N [auth B], O [auth B], P [auth B], Q [auth B]	HEGA-10 C₁₈ H₃₇ N O₇ ITEIKACYSCODFV-ATLSCFEFSA-N		Interactions Focus chain E [auth A] Focus chain F [auth A] Focus chain G [auth A] Focus chain H [auth A] Focus chain M [auth B] Focus chain N [auth B] Focus chain O [auth B] Focus chain P [auth B] Focus chain Q [auth B] Interactions & Density Focus chain E [auth A] Focus chain F [auth A] Focus chain G [auth A] Focus chain H [auth A] Focus chain M [auth B] Focus chain N [auth B] Focus chain O [auth B] Focus chain P [auth B] Focus chain Q [auth B]
XF5 Query on XF5 Download Ideal Coordinates CCD File SDF format, chain I [auth A] SDF format, chain S [auth B] MOL2 format, chain I [auth A] MOL2 format, chain S [auth B] mmCIF format, chain I [auth A] mmCIF format, chain S [auth B]	I [auth A], S [auth B]	4-(PIPERAZIN-1-YL)-1H-INDOLE C₁₂ H₁₅ N₃ YZKSXUIOKWQABW-UHFFFAOYSA-N		Interactions Focus chain I [auth A] Focus chain S [auth B] Interactions & Density Focus chain I [auth A] Focus chain S [auth B]
NA Query on NA Download Ideal Coordinates CCD File SDF format, chain J [auth A] SDF format, chain R [auth B] SDF format, chain T [auth B] MOL2 format, chain J [auth A] MOL2 format, chain R [auth B] MOL2 format, chain T [auth B] mmCIF format, chain J [auth A] mmCIF format, chain R [auth B] mmCIF format, chain T [auth B]	J [auth A], R [auth B], T [auth B]	SODIUM ION Na FKNQFGJONOIPTF-UHFFFAOYSA-N		Interactions Focus chain J [auth A] Focus chain R [auth B] Focus chain T [auth B] Interactions & Density Focus chain J [auth A] Focus chain R [auth B] Focus chain T [auth B]

Binding Affinity Annotations
ID	Source	Binding Affinity
XF5	PDBBind: 3ZPQ	Ki: 67.6 (nM) from 1 assay(s)

Experimental Data & Validation

Experimental Data

Method: X-RAY DIFFRACTION
Resolution: 2.80 Å
R-Value Free: 0.274
R-Value Work: 0.220
R-Value Observed: 0.223
Space Group: P 1 2₁ 1

Unit Cell:

Length ( Å )	Angle ( ˚ )
a = 89.852	α = 90
b = 61.441	β = 108.89
c = 100.784	γ = 90

Software Package:

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

Structure Validation

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Ligand Structure Quality Assessment

Entry History

Deposition Data

Released Date: 2013-04-03

Deposition Author(s):

Revision History (Full details and data files)

Version 1.0: 2013-04-03
Type: Initial release
Version 1.1: 2013-05-22
Changes: Database references
Version 1.2: 2019-04-03
Changes: Data collection, Other, Source and taxonomy
Version 1.3: 2019-05-15
Changes: Data collection, Experimental preparation
Version 1.4: 2023-12-20
Changes: Data collection, Database references, Derived calculations, Other, Refinement description
Version 1.5: 2024-11-13
Changes: Structure summary

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Help and Resources

3ZPQ

Thermostabilised turkey beta1 adrenergic receptor with 4-(piperazin-1- yl)-1H-indole bound (compound 19)

Biophysical Fragment Screening of the Beta1-Adrenergic Receptor: Identification of High Affinity Aryl Piperazine Leads Using Structure-Based Drug Design.

Entity ID: 1

UniProt

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)