Gaqproteins: molecular pharmacology and therapeutic potential.
Seven transmembrane G protein-coupled receptors (GPCRs) have gained much interest in recent years as it is the largest class among cell surface receptors. G proteins lie in the heart of GPCRs signalling and therefore can be therapeutically targeted to overcome complexities in GPCR responses and signalling. G proteins are classified into four families (Gi, Gs, G12/13and Gq); Gqis further subdivided into four classes. Among them Gαqand Gαq/11isoforms are most crucial and ubiquitously expressed; these isoforms are almost 88% similar at their amino acid sequence but may exhibit functional divergences. However, uncertainties often arise about Gαqand Gαq/11inhibitors, these G proteins might also have suitability to the invention of novel-specific inhibitors for each isoforms. YM-254890 and UBO-QIC are discovered as potent inhibitors of Gαqfunctions and also investigated in thrombin protease-activated receptor (PAR)-1 inhibitors and platelet aggregation inhibition. The most likely G protein involved in PAR-1 stimulates responses is one of the Gαqfamily isoforms. In this review, we highlight the molecular structures and pharmacological responses of Gαqfamily which may reflect the biochemical and molecular role of Gαqand Gαq/11. The advanced understanding of Gαqand Gαq/11role in GPCR signalling may shed light on our understanding on cell biology, cellular physiology and pathophysiology and also lead to the development of novel therapeutic agents for a number of diseases.
School of Pharmacy, Pharmacy Australia Centre of Excellence, The University of Queensland, 20 Cornwall Street, Woolloongabba, QLD, 4102, Australia.
Danielle
D
Kamato
School of Pharmacy, Pharmacy Australia Centre of Excellence, The University of Queensland, 20 Cornwall Street, Woolloongabba, QLD, 4102, Australia.
Partha
P
Mitra
School of Pharmacy, Pharmacy Australia Centre of Excellence, The University of Queensland, 20 Cornwall Street, Woolloongabba, QLD, 4102, Australia.
Felicity
F
Davis
School of Pharmacy, Pharmacy Australia Centre of Excellence, The University of Queensland, 20 Cornwall Street, Woolloongabba, QLD, 4102, Australia.|School of Medical Sciences, RMIT University, Bundoora, VIC, 3083, Australia.|Department of Immunology, Monash University, Melbounre, VIC, 3004, Australia.
Narin
N
Osman
School of Pharmacy, Pharmacy Australia Centre of Excellence, The University of Queensland, 20 Cornwall Street, Woolloongabba, QLD, 4102, Australia.
Rebecca
R
Chaplin
School of Pharmacy, Pharmacy Australia Centre of Excellence, The University of Queensland, 20 Cornwall Street, Woolloongabba, QLD, 4102, Australia.
Peter J
PJ
Cabot
Department of Biochemistry, Primeasia University, Banani, 1213, Bangladesh.
Rizwana
R
Afroz
School of Biomedical Sciences, The University of Queensland, St. Lucia, QLD, 4102, Australia.
Walter
W
Thomas
Faculty of Health Sciences, University of Macau, Taipa, Macau, China.
Wenhua
W
Zheng
Department of Chemistry, School of Biological Sciences, University of Auckland, Auckland, New Zealand.
Harveen
H
Kaur
Department of Chemistry, School of Biological Sciences, University of Auckland, Auckland, New Zealand.
Margaret
M
Brimble
School of Pharmacy, Pharmacy Australia Centre of Excellence, The University of Queensland, 20 Cornwall Street, Woolloongabba, QLD, 4102, Australia. p.little@uq.edu.au.|School of Medical Sciences, RMIT University, Bundoora, VIC, 3083, Australia. p.little@uq.edu.au.|Xinhua College of Sun Yat-sen University, Tianhe District, Guangzhou, 510520, China. p.little@uq.edu.au.
Peter J
PJ
Little
D000595:Amino Acid Sequence; D000818:Animals; D047630:Depsipeptides / Q000494:pharmacology*; D055808:Drug Discovery; D043802:GTP-Binding Protein alpha Subunits, Gq-G11 / Q000032:analysis / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D019204:GTP-Binding Proteins / Q000378:metabolism; D006801:Humans; D008958:Models, Molecular; D010456:Peptides, Cyclic / Q000494:pharmacology*; D011487:Protein Conformation; D020033:Protein Isoforms / Q000032:analysis / Q000037:antagonists & inhibitors / Q000378:metabolism; D016415:Sequence Alignment; D015398:Signal Transduction / Q000187:drug effects*
D047630:Depsipeptides; C000607068:FR900359; D010456:Peptides, Cyclic; D020033:Protein Isoforms; C475455:YM-254890; D019204:GTP-Binding Proteins; D043802:GTP-Binding Protein alpha Subunits, Gq-G11
Atherosclerosis; G Protein-coupled receptors; G alpha q; G proteins; GPCRs; Hyperelongation; Isoforms; PAR-1