3ZPR

Thermostabilised turkey beta1 adrenergic receptor with 4-methyl-2-(piperazin-1-yl) quinoline bound

Summary for 3ZPR

• Entry DOI: 10.2210/pdb3zpr/pdb
• Related: 3ZPQ
• Descriptor: BETA-1 ADRENERGIC RECEPTOR, SODIUM ION, CHOLESTEROL HEMISUCCINATE, ... (6 entities in total)
• Functional Keywords: membrane protein, gpcr, fragment screening, aryl piperazine, structure based drug design
• Biological source: MELEAGRIS GALLOPAVO (TURKEY)
• Total number of polymer chains: 2
• Total formula weight: 77410.94

Authors

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. (deposition date: 2013-03-01, release date: 2013-04-03, Last modification date: 2024-10-23)

Primary citation

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.
Biophysical Fragment Screening of the Beta1-Adrenergic Receptor: Identification of High Affinity Aryl Piperazine Leads Using Structure-Based Drug Design.
J.Med.Chem., 56:3446-, 2013

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.

PubMed: 23517028
DOI: 10.1021/JM400140Q

Experimental method

X-RAY DIFFRACTION (2.7 Å)