PDBsum entry 6ps1

Membrane protein

PDB id: 6ps1

Contents

Protein chain

442 a.a.

Ligands

TIM

SO4 ×3

CLR

OLC ×2

OLA

PDB id:

6ps1

Name:

Membrane protein

Title:

Xfel beta2 ar structure by ligand exchange from alprenolol to timolol.

Structure:

Fusion protein of beta-2 adrenergic receptor and t4 lysozyme. Chain: a. Synonym: beta-2 adrenoreceptor,beta-2 adrenoceptor,lysis protein, lysozyme,muramidase. Engineered: yes

Source:

Homo sapiens, enterobacteria phage t4. Human. Organism_taxid: 9606, 10665. Gene: adrb2, adrb2r, b2ar, e, t4tp126. Expressed in: spodoptera frugiperda. Expression_system_taxid: 7108.

Resolution:

3.20Å R-factor: 0.230 R-free: 0.264

Authors:

A.Ishchenko,B.Stauch,G.W.Han,A.Batyuk,A.Shiriaeva,C.Li,N.A.Zatsepin, U.Weierstall,W.Liu,E.Nango,T.Nakane,R.Tanaka,K.Tono,Y.Joti,S.Iwata, I.Moraes,C.Gati,C.Cherezov

Key ref:

A.Ishchenko et al. (2019). Toward G protein-coupled receptor structure-based drug design using X-ray lasers. IUCrJ, 6, 1106-1119. PubMed id: 31709066 DOI: 10.1107/S2052252519013137

Date:

12-Jul-19 Release date: 13-Nov-19

Protein chain

D9IEF7  (D9IEF7_BPT4) -  Endolysin from Enterobacteria phage T4

Seq: 164 a.a.

Struc: 442 a.a.*

Protein chain

P07550  (ADRB2_HUMAN) -  Beta-2 adrenergic receptor from Homo sapiens

Seq: 413 a.a.

Struc: 442 a.a.*

* PDB and UniProt seqs differ at 155 residue positions (black crosses)

Enzyme reactions

• Enzyme class: E.C.3.2.1.17 - lysozyme.
• Reaction: Hydrolysis of the 1,4-beta-linkages between N-acetyl-D-glucosamine and N-acetylmuramic acid in peptidoglycan heteropolymers of the prokaryotes cell walls.

DOI no: 10.1107/S2052252519013137

IUCrJ 6:1106-1119 (2019)

PubMed id: 31709066

Toward G protein-coupled receptor structure-based drug design using X-ray lasers.

A.Ishchenko, B.Stauch, G.W.Han, A.Batyuk, A.Shiriaeva, C.Li, N.Zatsepin, U.Weierstall, W.Liu, E.Nango, T.Nakane, R.Tanaka, K.Tono, Y.Joti, S.Iwata, I.Moraes, C.Gati, V.Cherezov.

ABSTRACT

Rational structure-based drug design (SBDD) relies on the availability of a large number of co-crystal structures to map the ligand-binding pocket of the target protein and use this information for lead-compound optimization via an iterative process. While SBDD has proven successful for many drug-discovery projects, its application to G protein-coupled receptors (GPCRs) has been limited owing to extreme difficulties with their crystallization. Here, a method is presented for the rapid determination of multiple co-crystal structures for a target GPCR in complex with various ligands, taking advantage of the serial femtosecond crystallography approach, which obviates the need for large crystals and requires only submilligram quantities of purified protein. The method was applied to the human β₂-adrenergic receptor, resulting in eight room-temperature co-crystal structures with six different ligands, including previously unreported structures with carvedilol and propranolol. The generality of the proposed method was tested with three other receptors. This approach has the potential to enable SBDD for GPCRs and other difficult-to-crystallize membrane proteins.