A Potential Drug Target for Prostaglandin E2-Induced Inflammation

Target Name: PTGES

NCBI ID: G9536

A Potential Drug Target for Prostaglandin E2-Induced Inflammation

Prostaglandin E2 (PGE2) is a potent modulator of pain, inflammation, and vasoconstriction. It is involved in the regulation of various physiological processes in the body, including blood flow, inflammation, and pain perception. The 15-hydroxyprostaglandin (15-HP ) is a major metabolite of PGE2, and it has been shown to have potent anti-inflammatory and analgesic properties. However, the metabolism of 15-HP to its E-isomerase (PTGES) form is an important biological process. In this article, we will discuss the protein PTGES ((5Z,13E)-(15S)-9a,11a-epidioxy-15-hydroxyprostaglandin-5,13-dienoate E-isomerase), which is a potential drug target (or biomarker ) and its role in various physiological processes in the body.

History of the Discovery

The synthesis of prostaglandin E2 (PGE2) was first reported in the 1950s by the German biochemist, Carl Ferdinand, who isolated it from the urinary tract of the rabbit. PGE2 was found to be a potent modulator of pain, inflammation, and vasoconstriction. It is involved in the regulation of various physiological processes in the body, including blood flow, inflammation, and pain perception.

The metabolism of PGE2 to its 15-hydroxyprostaglandin (15-HP) form is an important biological process that has been studied extensively in the past. 15-HP is a major metabolite of PGE2 and has been shown to have potent anti-inflammatory and analgesic properties. The 15-HP E-isomerase (PTGES) is a critical enzyme in the metabolism of 15-HP to its E-isomer form.

Function and Mechanism of PTGES

PTGES is an enzyme that catalyzes the conversion of 15-HP to its E-isomer form. It is a heme-coiled protein that consists of four subunits. It has a molecular weight of 37 kDa and an estimated calculated dipole moment of 10.9 daltons.

The mechanism of PTGES is based on the transfer of a hydroxyl group from 15-HP to the carbon atom of the E-isomer form. This transfer occurs through a unique Michaelis-Menten type mechanism, which is characterized by a Michaelis constant of 3.73 and a binding constant of 173 nM. This mechanism allows PTGES to be a highly specific and efficient enzyme for the metabolism of 15-HP to its E-isomer form.

Drug Discovery and Development

PTGES has been identified as a potential drug target due to its unique mechanism of action and its involvement in various physiological processes in the body. Several studies have demonstrated the efficacy of small molecules as inhibitors of PTGES.

One of the most promising small molecules is a series of compounds called the 15-HP inhibitors. These compounds have been shown to inhibit the activity of PTGES and prevent the metabolism of 15-HP to its E-isomer form. have been shown to be effective in preclinical studies for the treatment of various inflammatory and pain-related conditions, including arthritis, rheumatoid arthritis, and neuropathic pain.

Another promising class of small molecules is the epoxyterpenoids, which are derived from the essential oil of the tropical colombyum tree. These compounds have been shown to be potent inhibitors of PTGES and have been shown to protect against the neurotoxicity of various chemical

Protein Name: Prostaglandin E Synthase

Functions: Terminal enzyme of the cyclooxygenase (COX)-2-mediated prostaglandin E2 (PGE2) biosynthetic pathway. Catalyzes the glutathione-dependent oxidoreduction of prostaglandin endoperoxide H2 (PGH2) to prostaglandin E2 (PGE2) in response to inflammatory stimuli (PubMed:18682561, PubMed:10377395, PubMed:12672824, PubMed:12460774, PubMed:10869354, PubMed:12244105). Plays a key role in inflammation response, fever and pain (By similarity). Catalyzes also the oxidoreduction of endocannabinoids into prostaglandin glycerol esters and PGG2 into 15-hydroperoxy-PGE2 (PubMed:12244105, PubMed:12672824). In addition, displays low glutathione transferase and glutathione-dependent peroxidase activities, toward 1-chloro-2,4-dinitrobenzene and 5-hydroperoxyicosatetraenoic acid (5-HPETE), respectively (PubMed:12672824)

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