LTC4 synthase

Compound 508 (PNRI-299), a small molecule /3-strand mimetic template compound, is active as an inhibitor of the multifunctional activating protein factor 1 (AP-1). PNRI-299 has demonstrable effects on the reduction of API-driven transcription and beneficial pharmacological effects in a mouse asthma model. The compound affects the expression of leukotriene C4 (LTC4) synthase, a crucial enzyme for the formation of the cysteinyl leukotrienes <2003PNA1169, 2004MI211>. 

Anderson W, Kalberg C, Edwards L et al. Effects of polymorphisms in the promoter region of 5-lipoxygenase and LTC4 synthase on the clinical response to Za-firlukast and Fluticasone. Eur Respir J 2000 16 183s. 

Chong T, McMillan M, Teo JL, Henderson WR Jr., Kahn M. Chemogenomic investigation of AP-1 transcriptional regnla-tion of LTC4 synthase expression. Lett. Drug Design Discov. 2004 1 211-216. 

FLAP likely exists as a homodimer or possibly a heterodimer with LTC4 synthase. 

LTC4 synthase. The mechanism by which 5-LO is trafficked to the nuclear membrane is controlled by the C2-like domain of 5-LO that binds two Ca " " ions which imparts high affinity for glycerophosphocholine lipids rich on the outer leaflet of either nuclear membrane [25]. 5-LO can be phosphorylated at S271 (MAPKAP kinase dependent) and S663 (ERK-1/2 dependent) to increase 5-LO activity and direct trafficking of 5-LO to the nucleoplasm. However, phosphorylation of S523, a protein kinase A-dependent process, inhibits 5-LO activity (see below). 

---