PDBsum entry 7bvq

Membrane protein

PDB id: 7bvq

Contents

Protein chains

455 a.a.

Ligands

GLC-GLC

CLR

CAU ×2

SO4 ×8

1WV ×2

CIT ×2

PG4 ×4

Metals

_NA

Waters ×121

PDB id:

7bvq

Name:

Membrane protein

Title:

Structure of human beta1 adrenergic receptor bound to carazolol

Structure:

Endolysin,beta-1 adrenergic receptor chimera. Chain: a, b. Synonym: lysozyme,muramidase. Engineered: yes. Mutation: yes. Other_details: 1261 cys to 1314 leu are truncated region.,1261 cys to 1314 leu are truncated region.

Source:

Enterobacteria phage t4, homo sapiens. Organism_taxid: 10665, 9606. Gene: e, t4tp126. Expressed in: spodoptera frugiperda. Expression_system_taxid: 7108

Resolution:

2.50Å R-factor: 0.227 R-free: 0.263

Authors:

X.Xu,J.Kaindl,M.Clark,H.Hubner,K.Hirata,R.Sunahara,P.Gmeiner, B.K.Kobilka,X.Liu

Key ref:

X.Xu et al. (2021). Binding pathway determines norepinephrine selectivity for the human β₁AR over β₂AR. Cell Res, 31, 569-579. PubMed id: 33093660 DOI: 10.1038/s41422-020-00424-2

Date:

11-Apr-20 Release date: 02-Dec-20

Protein chains

D9IEF7  (D9IEF7_BPT4) -  Endolysin from Enterobacteria phage T4

Seq: 164 a.a.

Struc: 455 a.a.*

Protein chains

P08588  (ADRB1_HUMAN) -  Beta-1 adrenergic receptor from Homo sapiens

Seq: 477 a.a.

Struc: 455 a.a.*

* PDB and UniProt seqs differ at 55 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: 10.1038/s41422-020-00424-2

Cell Res 31:569-579 (2021)

PubMed id: 33093660

Binding pathway determines norepinephrine selectivity for the human β₁AR over β₂AR.

X.Xu, J.Kaindl, M.J.Clark, H.Hübner, K.Hirata, R.K.Sunahara, P.Gmeiner, B.K.Kobilka, X.Liu.

ABSTRACT

Beta adrenergic receptors (βARs) mediate physiologic responses to the catecholamines epinephrine and norepinephrine released by the sympathetic nervous system. While the hormone epinephrine binds β₁AR and β₂AR with similar affinity, the smaller neurotransmitter norepinephrine is approximately tenfold selective for the β₁AR. To understand the structural basis for this physiologically important selectivity, we solved the crystal structures of the human β₁AR bound to an antagonist carazolol and different agonists including norepinephrine, epinephrine and BI-167107. Structural comparison revealed that the catecholamine-binding pockets are identical between β₁AR and β₂AR, but the extracellular vestibules have different shapes and electrostatic properties. Metadynamics simulations and mutagenesis studies revealed that these differences influence the path norepinephrine takes to the orthosteric pocket and contribute to the different association rates and thus different affinities.