PDBsum entry 6k1q

Signaling protein

PDB id: 6k1q

Contents

Protein chain

410 a.a.

Ligands

D2U

PO4 ×4

OLC ×8

Waters ×34

PDB id:

6k1q

Name:

Signaling protein

Title:

Human endothelin receptor type-b in complex with inverse agonist irl2500

Structure:

Endothelin b receptor,endolysin,endothelin b receptor. Chain: a. Synonym: et-br,endothelin receptor non-selective type,lysis protein, lysozyme,muramidase,et-br,endothelin receptor non-selective type. Engineered: yes. Mutation: yes

Source:

Homo sapiens, enterobacteria phage t4. Human. Organism_taxid: 9606, 10665. Gene: ednrb, etrb. Expressed in: spodoptera frugiperda. Expression_system_taxid: 7108. Expression_system_cell_line: sf9.

Resolution:

2.70Å R-factor: 0.224 R-free: 0.265

Authors:

C.Nagiri,W.Shihoya,O.Nureki

Key ref:

C.Nagiri et al. (2019). Crystal structure of human endothelin ET_B receptor in complex with peptide inverse agonist IRL2500. Commun Biol, 2, 236. PubMed id: 31263780 DOI: 10.1038/s42003-019-0482-7

Date:

11-May-19 Release date: 17-Jul-19

Protein chain

P00720  (ENLYS_BPT4) -  Endolysin from Enterobacteria phage T4

Seq: 164 a.a.

Struc: 410 a.a.*

Protein chain

P24530  (EDNRB_HUMAN) -  Endothelin receptor type B from Homo sapiens

Seq: 442 a.a.

Struc: 410 a.a.*

* PDB and UniProt seqs differ at 175 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/s42003-019-0482-7

Commun Biol 2:236 (2019)

PubMed id: 31263780

Crystal structure of human endothelin ET_B receptor in complex with peptide inverse agonist IRL2500.

C.Nagiri, W.Shihoya, A.Inoue, F.M.N.Kadji, J.Aoki, O.Nureki.

ABSTRACT

Endothelin receptors (ET_A and ET_B) are G-protein-coupled receptors activated by endothelin-1 and are involved in blood pressure regulation. IRL2500 is a peptide-mimetic of the C-terminal tripeptide of endothelin-1, and has been characterized as a potent ET_B-selective antagonist, which has preventive effects against brain edema. Here, we report the crystal structure of the human ET_B receptor in complex with IRL2500 at 2.7 Å-resolution. The structure revealed the different binding modes between IRL2500 and endothelin-1, and provides structural insights into its ET_B-selectivity. Notably, the biphenyl group of IRL2500 penetrates into the transmembrane core proximal to D^2.50, thus stabilizing the inactive conformation. Using the newly-established constitutively active mutant, we clearly demonstrate that IRL2500 functions as an inverse agonist for the ET_B receptor. The current findings will expand the chemical space of ETR antagonists and facilitate the design of inverse agonists for other class A GPCRs.