NMR structure of the thromboxane A2 receptor ligand recognition pocket

European Journal of Biochemistry
Ke-He RuanCheng-Huai Ruan

Abstract

To overcome the difficulty of characterizing the structures of the extracellular loops (eLPs) of G protein-coupled receptors (GPCRs) other than rhodopsin, we have explored a strategy to generate a three-dimensional structural model for a GPCR, the thromboxane A(2) receptor. This three-dimensional structure was completed by the assembly of the NMR structures of the computation-guided constrained peptides that mimicked the extracellular loops and connected to the conserved seven transmembrane domains. The NMR structure-based model reveals the structural features of the eLPs, in which the second extracellular loop (eLP(2)) and the disulfide bond between the first extracellular loop (eLP(1)) and eLP(2) play a major role in forming the ligand recognition pocket. The eLP(2) conformation is dynamic and regulated by the oxidation and reduction of the disulfide bond, which affects ligand docking in the initial recognition. The reduced form of the thromboxane A(2) receptor experienced a decrease in ligand binding activity due to the rearrangement of the eLP(2) conformation. The ligand-bound receptor was, however, resistant to the reduction inactivation because the ligand covered the disulfide bond and stabilized the eLP(2) conformation. ...Continue Reading

References

Dec 1, 1990·Journal of Protein Chemistry·S SakataK Miura
Jun 20, 1990·Journal of Molecular Biology·R HendersonK H Downing
Jan 1, 1989·Methods in Enzymology·V J Basus
Sep 1, 1989·Proceedings of the National Academy of Sciences of the United States of America·B KönigK P Hofmann
Oct 26, 1995·Biochimica Et Biophysica Acta·M NegishiA Ichikawa
Oct 1, 1995·Nature Structural Biology·P L YeagleA D Albert
Nov 14, 1995·Biochemistry·P L YeagleA D Albert
Aug 1, 1994·Current Opinion in Biotechnology·T W Schwartz
Apr 2, 1993·Journal of Medicinal Chemistry·Y YamamotoS Terao
Jun 14, 1996·Journal of Molecular Biology·N GrigorieffR Henderson
Jul 4, 1998·The Journal of Biological Chemistry·T H JiI Ji
Aug 5, 2000·Science·K PalczewskiM Miyano
Mar 6, 2002·The Journal of Biological Chemistry·Joseph W TurekGuy C Le Breton
Jun 5, 2003·Archives of Biochemistry and Biophysics·Jiaxin WuKe-He Ruan

❮ Previous
Next ❯

Citations

Aug 9, 2011·Chemical Reviews·Takako Hirata, Shuh Narumiya
Aug 19, 2007·Journal of the American Chemical Society·Youyong LiAbdelazize Laoui
Oct 1, 2006·Expert Opinion on Drug Discovery·Adriano Martinelli, Tiziano Tuccinardi
Jan 8, 2008·Biochimica Et Biophysica Acta·Monika Musial-SiwekPhilip L Yeagle
Nov 14, 2006·Biochimica Et Biophysica Acta·Philip L Yeagle, Arlene D Albert
Oct 8, 2016·PloS One·Clive MetcalfeCarmen H Coxon
Jun 25, 2018·Journal of the American Heart Association·Firdos Ahmad
Jun 25, 2018·Journal of the American Heart Association·Fatima Z AlshboolFadi T Khasawneh
Jul 11, 2006·Magnetic Resonance in Chemistry : MRC·Charles R Sanders, Frank Sönnichsen

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.