Prostaglandin E synthase

Function

Microsomal Prostaglandin E synthase (PGES) converts cyclooxygenase (COX)-derived prostaglandin to PGE2. It is membrane-associated and belongs to the microsomal glutathione S-transferase family. PGES is preferentially linked with the inducible COX-2^[1] . PGES is induced by proinflammatory stimuli and down-regulated by anti-inflammatory glucocorticoids^[2].

Relevance

PGES participates in several pathophysiological states in which COX-2 is involved and hence represents a potential target for anti-inflammatory and anti-cancer drug development^[3] .

Structural highlights

The anti-inflammatory inhibitor binds to PGES in a pocket above the glutathione and interacts with various side-chains of a helix^[4] .

3D Structures of prostaglandin E synthase3D Structures of prostaglandin E synthase

Updated on 18-January-2018

3dww, 4al0, 4wab, 4bpm – hPGES-1 + glutathione – human
4al1 – hPGES-1 + glutathione analog
5bqg, 5bqh, 5bqi, 5k0i, 5t36, 5t37, 5tl9, 4yk5, 4yl0, 4yl1, 4yl3 – hPGES-1 + glutathione + inhibitor
1z9h – MaPGES-2 + indomethacin – Macaque
2pbj – MaPGES-2 + heme + glutathione

ReferencesReferences

↑ Murakami M, Nakatani Y, Tanioka T, Kudo I. Prostaglandin E synthase. Prostaglandins Other Lipid Mediat. 2002 Aug;68-69:383-99. PMID:12432931
↑ Kudo I, Murakami M. Prostaglandin E synthase, a terminal enzyme for prostaglandin E2 biosynthesis. J Biochem Mol Biol. 2005 Nov 30;38(6):633-8. PMID:16336776
↑ Murakami M, Kudo I. Prostaglandin E synthase: a novel drug target for inflammation and cancer. Curr Pharm Des. 2006;12(8):943-54. PMID:16533161
↑ Luz JG, Antonysamy S, Kuklish SL, Condon B, Lee MR, Allison D, Yu XP, Chandrasekhar S, Backer R, Zhang A, Russell M, Chang SS, Harvey A, Sloan AV, Fisher MJ. Crystal Structures of mPGES-1 Inhibitor Complexes Form a Basis for the Rational Design of Potent Analgesic and Anti-Inflammatory Therapeutics. J Med Chem. 2015 May 20. PMID:25961169 doi:http://dx.doi.org/10.1021/acs.jmedchem.5b00330

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Michal Harel, Alexander Berchansky, Joel L. Sussman

[1] Murakami M, Nakatani Y, Tanioka T, Kudo I. Prostaglandin E synthase. Prostaglandins Other Lipid Mediat. 2002 Aug;68-69:383-99. PMID:12432931

[2] Kudo I, Murakami M. Prostaglandin E synthase, a terminal enzyme for prostaglandin E2 biosynthesis. J Biochem Mol Biol. 2005 Nov 30;38(6):633-8. PMID:16336776

[3] Murakami M, Kudo I. Prostaglandin E synthase: a novel drug target for inflammation and cancer. Curr Pharm Des. 2006;12(8):943-54. PMID:16533161

[4] Luz JG, Antonysamy S, Kuklish SL, Condon B, Lee MR, Allison D, Yu XP, Chandrasekhar S, Backer R, Zhang A, Russell M, Chang SS, Harvey A, Sloan AV, Fisher MJ. Crystal Structures of mPGES-1 Inhibitor Complexes Form a Basis for the Rational Design of Potent Analgesic and Anti-Inflammatory Therapeutics. J Med Chem. 2015 May 20. PMID:25961169 doi:http://dx.doi.org/10.1021/acs.jmedchem.5b00330

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