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PMID: 12825452 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. Review

G protein-coupled receptor drug discovery: implications from the crystal structure of rhodopsin.

Current opinion in drug discovery & development ·Vol. 4 ·No. 5 ·2001-09-00 ·Pages 561-74

Ballesteros J, Palczewski K

Abstract

G protein-coupled receptors (GPCRs) are a functionally diverse group of membrane proteins that play a critical role in signal transduction. Because of the lack of a high-resolution structure, the heptahelical transmembrane bundle within the N-terminal extracellular and C-terminal intracellular region of these receptors has initially been modeled based on the high-resolution structure of bacterial retinal-binding protein, bacteriorhodopsin. However, the low-resolution structure of rhodopsin, a prototypical GPCR, revealed that there is a minor relationship between GPCRs and bacteriorhodopsins. The high-resolution crystal structure of the rhodopsin ground state and further refinements of the model provide the first structural information about the entire organization of the polypeptide chain and post-translational moieties. These studies provide a structural template for Family 1 GPCRs that has the potential to significantly improve structure-based approaches to GPCR drug discovery.

MeSH Terms
Amino Acid Sequence Animals Crystallography, X-Ray Drug Design GTP-Binding Proteins/chemistry Humans Models, Molecular Molecular Sequence Data Receptors, Drug/chemistry Rhodopsin/chemistry
Chemicals
Receptors, Drug Rhodopsin GTP-Binding Proteins
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Ballesteros J
Novasite Pharmaceuticals Inc., 3520 Dunhill Street, San Diego, CA 92121, USA. jballesteros@novasite.com
Palczewski K
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Article Info
Journal
Current opinion in drug discovery & development
Abbr.
Curr Opin Drug Discov Devel
ISSN
1367-6733
Email
jballesteros@novasite.com
Published
2001-09-00
Pages
561-74
Language
English
Region
England
NLM ID
100887519
PMCID
PMC1383658
Subset
IM
Grants
NEI NIH HHS · R01 EY008061 · United States
NIAID NIH HHS · AI48517 · United States
NEI NIH HHS · EY08061 · United States
External Links
PubMed source PMC Full Text View journal details
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