Heterotrimeric G-proteins mediate between receptors and effectors, acting as molecular clocks. G-protein interactions with activated receptors catalyze the replacement of GDP bound to the alpha-subunit with GTP. alpha-Subunits then modulate the activity of downstream effectors until the bound GTP is hydrolyzed. In several signal transduction pathways, including the cGMP cascade of photoreceptor cells, the relatively slow GTPase activity of heterotrimeric G-proteins can be significantly accelerated when they are complexed with corresponding effectors. In the phototransduction cascade the GTPase activity of photoreceptor G-protein, transducin, is substantially accelerated in a complex with its effector, cGMP phosphodiesterase. Here we characterize the stimulation of transducin GTPase by a set of 23 mutant phosphodiesterase gamma-subunits (PDE gamma) containing single alanine substitutions within a stretch of the 25 C-terminal amino acid residues known to be primarily responsible for the GTPase regulation. The substitution of tryptophan at position 70 completely abolished the acceleration of GTP hydrolysis by transducin in a complex with this mutant. This mutation also resulted in a reduction of PDE gamma affinity for transducin, but did not affect PDE gamma interactions with the phosphodiesterase catalytic subunits. Single substitutions of 7 other hydrophobic amino acids resulted in a 50-70% reduction in the ability of PDE gamma to stimulate transducin GTPase, while substitutions of charged and polar amino acids had little or no effect. These observations suggest that the role of PDE gamma in activation of the transducin GTPase rate may be based on multiple hydrophobic interactions between these molecules.
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http://dx.doi.org/10.1074/jbc.270.24.14319 | DOI Listing |
Life Sci
January 2025
Pharmacology and Toxicology Laboratory, Dietetics and Nutrition Technology Division, CSIR-Institute of Himalayan Bioresource Technology, Palampur 176061, Himachal Pradesh, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, India. Electronic address:
Aims: Hyperammonaemia (HA) is a metabolic disorder characterized by increased ammonia levels in the blood and is associated with severe neurological impairments. Some previous findings have shown the involvement of the nitric oxide pathway in HA-induced neurological impairments. The current study explored the impact of tadalafil on neurological impairments induced by HA in a zebrafish larval model due to its reported indirect interactions with the nitric oxide pathway.
View Article and Find Full Text PDFPLoS Comput Biol
October 2024
Genomic Medicine Institute, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, United States of America.
J Ethnopharmacol
January 2025
Biochemical Toxicology, Biochemical Pharmacology, Reproductive Biochemistry and Phytomedicine Research Laboratory (BTBPRB&P-RL), Department of Biochemistry, University of Ilorin, Ilorin, Nigeria. Electronic address:
BMC Complement Med Ther
July 2024
Department of Pharmacognosy, Faculty of Pharmacy, Alexandria University, Alexandria, 21521, Egypt.
Background: Onion waste was reported to be a valuable source of bioactive constituents with potential health-promoting benefits. This sparked a surge of interest among scientists for its valorization. This study aims to investigate the chemical profiles of peel and root extracts of four onion cultivars (red, copper-yellow, golden yellow and white onions) and evaluate their erectogenic and anti-inflammatory potentials.
View Article and Find Full Text PDFJ Venom Anim Toxins Incl Trop Dis
May 2024
Queen Saovabha Memorial Institute, The Thai Red Cross Society, Pathumwan, Bangkok, Thailand.
Background: This study examines the direct nephrotoxic effects of venom (RVV) and venom fractions in and isolated perfused kidneys (IPK) to understand the role of inflammation pathways and susceptibility to oxidative stress in venom or fraction-induced acute renal failure.
Methods: We administered RVV and its venom fractions (PLA, MP, LAAO, and PDE) to rabbits and in the IPK model. We measured oxidative stress biomarkers (SOD, CAT, GSH, and MDA) in kidney tissue, as well as inflammatory cytokines (TNF-α, IL-1β, IFN-γ, IL-4, IL-5, and IL-10), MDA and GSH levels in plasma and urine.
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