Cannabinoid Interactions with Proteins

Insights from Structural Studies

Research output: Chapter in Book/Report/Conference proceedingChapter

Abstract

Cannabinoids have been widely used for recreational and medicinal purposes. The increasing legalization of cannabinoid use and the growing success in Medicinal Chemistry of cannabinoids have fueled recent interest in cannabinoid-sensing sites in receptor proteins. Here, we review structural data from high-resolution cryo-EM and crystallography studies that depict phytocannabinoid, endocannabinoid, and synthetic cannabinoid molecules bound to various proteins. The latter include antigen-binding fragment (Fab), cellular retinol binding protein 2 (CRBP2), fatty acid-binding protein 5 (FABP5), peroxisome proliferator-activated receptor γ (PPAR γ), and cannabinoid receptor types 1 and 2 (CB1 and CB2). Cannabinoid-protein complexes reveal the complex design of cannabinoid binding sites that are usually presented by conventional ligand-binding pockets on respective proteins. However, subtle differences in cannabinoid interaction with amino acids within the binding pocket often result in diverse consequences for protein function. The rapid increase in available structural data on cannabinoid-protein interactions will ultimately direct drug design efforts toward rendering highly potent cannabinoid-related pharmacotherapies that are devoid of side effects.

Original languageEnglish (US)
Title of host publicationAdvances in Experimental Medicine and Biology
PublisherSpringer New York LLC
Pages39-50
Number of pages12
DOIs
StatePublished - Jan 1 2019

Publication series

NameAdvances in Experimental Medicine and Biology
Volume1162
ISSN (Print)0065-2598
ISSN (Electronic)2214-8019

Fingerprint

Cannabinoid Receptor Antagonists
Cannabinoid Receptor Agonists
Dronabinol
Cannabinoids
G-Protein-Coupled Receptors
Proteins
Cellular Retinol-Binding Proteins
2-arachidonylglycerol
anandamide
Drug therapy
Cannabinoid Receptors
Fatty Acid-Binding Proteins
Endocannabinoids
Immunoglobulin Fab Fragments
Crystallography
Pharmaceutical Chemistry
PPAR gamma
Drug Design
Switzerland
Binding Sites

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Bukiya, A., & Dopico, A. (2019). Cannabinoid Interactions with Proteins: Insights from Structural Studies. In Advances in Experimental Medicine and Biology (pp. 39-50). (Advances in Experimental Medicine and Biology; Vol. 1162). Springer New York LLC. https://doi.org/10.1007/978-3-030-21737-2_3

Cannabinoid Interactions with Proteins : Insights from Structural Studies. / Bukiya, Anna; Dopico, Alejandro.

Advances in Experimental Medicine and Biology. Springer New York LLC, 2019. p. 39-50 (Advances in Experimental Medicine and Biology; Vol. 1162).

Research output: Chapter in Book/Report/Conference proceedingChapter

Bukiya, A & Dopico, A 2019, Cannabinoid Interactions with Proteins: Insights from Structural Studies. in Advances in Experimental Medicine and Biology. Advances in Experimental Medicine and Biology, vol. 1162, Springer New York LLC, pp. 39-50. https://doi.org/10.1007/978-3-030-21737-2_3
Bukiya A, Dopico A. Cannabinoid Interactions with Proteins: Insights from Structural Studies. In Advances in Experimental Medicine and Biology. Springer New York LLC. 2019. p. 39-50. (Advances in Experimental Medicine and Biology). https://doi.org/10.1007/978-3-030-21737-2_3
Bukiya, Anna ; Dopico, Alejandro. / Cannabinoid Interactions with Proteins : Insights from Structural Studies. Advances in Experimental Medicine and Biology. Springer New York LLC, 2019. pp. 39-50 (Advances in Experimental Medicine and Biology).
@inbook{fbd1d56e2fd24901b3063ed0604fffab,
title = "Cannabinoid Interactions with Proteins: Insights from Structural Studies",
abstract = "Cannabinoids have been widely used for recreational and medicinal purposes. The increasing legalization of cannabinoid use and the growing success in Medicinal Chemistry of cannabinoids have fueled recent interest in cannabinoid-sensing sites in receptor proteins. Here, we review structural data from high-resolution cryo-EM and crystallography studies that depict phytocannabinoid, endocannabinoid, and synthetic cannabinoid molecules bound to various proteins. The latter include antigen-binding fragment (Fab), cellular retinol binding protein 2 (CRBP2), fatty acid-binding protein 5 (FABP5), peroxisome proliferator-activated receptor γ (PPAR γ), and cannabinoid receptor types 1 and 2 (CB1 and CB2). Cannabinoid-protein complexes reveal the complex design of cannabinoid binding sites that are usually presented by conventional ligand-binding pockets on respective proteins. However, subtle differences in cannabinoid interaction with amino acids within the binding pocket often result in diverse consequences for protein function. The rapid increase in available structural data on cannabinoid-protein interactions will ultimately direct drug design efforts toward rendering highly potent cannabinoid-related pharmacotherapies that are devoid of side effects.",
author = "Anna Bukiya and Alejandro Dopico",
year = "2019",
month = "1",
day = "1",
doi = "10.1007/978-3-030-21737-2_3",
language = "English (US)",
series = "Advances in Experimental Medicine and Biology",
publisher = "Springer New York LLC",
pages = "39--50",
booktitle = "Advances in Experimental Medicine and Biology",

}

TY - CHAP

T1 - Cannabinoid Interactions with Proteins

T2 - Insights from Structural Studies

AU - Bukiya, Anna

AU - Dopico, Alejandro

PY - 2019/1/1

Y1 - 2019/1/1

N2 - Cannabinoids have been widely used for recreational and medicinal purposes. The increasing legalization of cannabinoid use and the growing success in Medicinal Chemistry of cannabinoids have fueled recent interest in cannabinoid-sensing sites in receptor proteins. Here, we review structural data from high-resolution cryo-EM and crystallography studies that depict phytocannabinoid, endocannabinoid, and synthetic cannabinoid molecules bound to various proteins. The latter include antigen-binding fragment (Fab), cellular retinol binding protein 2 (CRBP2), fatty acid-binding protein 5 (FABP5), peroxisome proliferator-activated receptor γ (PPAR γ), and cannabinoid receptor types 1 and 2 (CB1 and CB2). Cannabinoid-protein complexes reveal the complex design of cannabinoid binding sites that are usually presented by conventional ligand-binding pockets on respective proteins. However, subtle differences in cannabinoid interaction with amino acids within the binding pocket often result in diverse consequences for protein function. The rapid increase in available structural data on cannabinoid-protein interactions will ultimately direct drug design efforts toward rendering highly potent cannabinoid-related pharmacotherapies that are devoid of side effects.

AB - Cannabinoids have been widely used for recreational and medicinal purposes. The increasing legalization of cannabinoid use and the growing success in Medicinal Chemistry of cannabinoids have fueled recent interest in cannabinoid-sensing sites in receptor proteins. Here, we review structural data from high-resolution cryo-EM and crystallography studies that depict phytocannabinoid, endocannabinoid, and synthetic cannabinoid molecules bound to various proteins. The latter include antigen-binding fragment (Fab), cellular retinol binding protein 2 (CRBP2), fatty acid-binding protein 5 (FABP5), peroxisome proliferator-activated receptor γ (PPAR γ), and cannabinoid receptor types 1 and 2 (CB1 and CB2). Cannabinoid-protein complexes reveal the complex design of cannabinoid binding sites that are usually presented by conventional ligand-binding pockets on respective proteins. However, subtle differences in cannabinoid interaction with amino acids within the binding pocket often result in diverse consequences for protein function. The rapid increase in available structural data on cannabinoid-protein interactions will ultimately direct drug design efforts toward rendering highly potent cannabinoid-related pharmacotherapies that are devoid of side effects.

UR - http://www.scopus.com/inward/record.url?scp=85070237541&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85070237541&partnerID=8YFLogxK

U2 - 10.1007/978-3-030-21737-2_3

DO - 10.1007/978-3-030-21737-2_3

M3 - Chapter

T3 - Advances in Experimental Medicine and Biology

SP - 39

EP - 50

BT - Advances in Experimental Medicine and Biology

PB - Springer New York LLC

ER -