PDBsum entry 5zty

Membrane protein

PDB id: 5zty

Contents

Protein chain

449 a.a.

Ligands

9JU

OLA

OLC ×3

PEG ×2

EPE ×2

PG4

SO4 ×5

Waters ×49

PDB id:

5zty

Name:

Membrane protein

Title:

Crystal structure of human g protein coupled receptor

Structure:

G protein coupled receptor,t4 lysozyme,g protein coupled receptor. Chain: a. Fragment: unp residues 21-222,unp residues 1-161,unp residues 235- 352. Synonym: lysis protein,lysozyme. Engineered: yes. Mutation: yes

Source:

Homo sapiens, enterobacteria phage t4. Human, bacteriophage t4. Organism_taxid: 9606, 10665. Expressed in: spodoptera frugiperda. Expression_system_taxid: 7108

Resolution:

2.80Å R-factor: 0.226 R-free: 0.275

Authors:

X.T.Li,T.Hua,L.J.Wu,Z.J.Liu

Key ref:

X.Li et al. (2019). Crystal Structure of the Human Cannabinoid Receptor CB2. Cell, 176, 459. PubMed id: 30639103 DOI: 10.1016/j.cell.2018.12.011

Date:

05-May-18 Release date: 30-Jan-19

Protein chain

D9IEF7  (D9IEF7_BPT4) -  Endolysin from Enterobacteria phage T4

Seq: 164 a.a.

Struc: 449 a.a.*

Protein chain

P34972  (CNR2_HUMAN) -  Cannabinoid receptor 2 from Homo sapiens

Seq: 360 a.a.

Struc: 449 a.a.*

* PDB and UniProt seqs differ at 166 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: 10.1016/j.cell.2018.12.011

Cell 176:459 (2019)

PubMed id: 30639103

Crystal Structure of the Human Cannabinoid Receptor CB2.

X.Li, T.Hua, K.Vemuri, J.H.Ho, Y.Wu, L.Wu, P.Popov, O.Benchama, N.Zvonok, K.Locke, L.Qu, G.W.Han, M.R.Iyer, R.Cinar, N.J.Coffey, J.Wang, M.Wu, V.Katritch, S.Zhao, G.Kunos, L.M.Bohn, A.Makriyannis, R.C.Stevens, Z.J.Liu.

ABSTRACT

The cannabinoid receptor CB2 is predominately expressed in the immune system, and selective modulation of CB2 without the psychoactivity of CB1 has therapeutic potential in inflammatory, fibrotic, and neurodegenerative diseases. Here, we report the crystal structure of human CB2 in complex with a rationally designed antagonist, AM10257, at 2.8 Å resolution. The CB2-AM10257 structure reveals a distinctly different binding pose compared with CB1. However, the extracellular portion of the antagonist-bound CB2 shares a high degree of conformational similarity with the agonist-bound CB1, which led to the discovery of AM10257's unexpected opposing functional profile of CB2 antagonism versus CB1 agonism. Further structural analysis using mutagenesis studies and molecular docking revealed the molecular basis of their function and selectivity for CB2 and CB1. Additional analyses of our designed antagonist and agonist pairs provide important insight into the activation mechanism of CB2. The present findings should facilitate rational drug design toward precise modulation of the endocannabinoid system.