Squalene synthase

Function

Squalene synthase (SQS) catalyzes the conversion of 2 molecules of farnesyl pyrophosphate (FPP) to the isoprenoid squalene. SQS is part of the isoprenoid biosynthesis pathway. SQS catalysis is the first step in the sterols synthesis including cholesterol^[1].

• Dehydrosqualene synthase or phytene synthase catalyzes the condensation of farnesyl diphosphate producing presqualene diphosphate^[2].

Relevance

SQS inhibitors are tested for antihyperlipidemic and antiatherosclerotic agents^[3].

Structural highlights

The active site of SQS contains a substrate analog^[4]. Water molecules are shown as red spheres. Mg coordination site.

3D structures of squalene synthase

Squalene synthase 3D structures

References

1. ↑ Tansey TR, Shechter I. Squalene synthase: structure and regulation. Prog Nucleic Acid Res Mol Biol. 2001;65:157-95. PMID:11008488
2. ↑ Lin FY, Liu CI, Liu YL, Zhang Y, Wang K, Jeng WY, Ko TP, Cao R, Wang AH, Oldfield E. Mechanism of action and inhibition of dehydrosqualene synthase. Proc Natl Acad Sci U S A. 2010 Nov 23. PMID:21098670 doi:10.1073/pnas.1010907107
3. ↑ Kourounakis AP, Katselou MG, Matralis AN, Ladopoulou EM, Bavavea E. Squalene synthase inhibitors: An update on the search for new antihyperlipidemic and antiatherosclerotic agents. Curr Med Chem. 2011;18(29):4418-39. PMID:21864285
4. ↑ Shang N, Li Q, Ko TP, Chan HC, Li J, Zheng Y, Huang CH, Ren F, Chen CC, Zhu Z, Galizzi M, Li ZH, Rodrigues-Poveda CA, Gonzalez-Pacanowska D, Veiga-Santos P, de Carvalho TM, de Souza W, Urbina JA, Wang AH, Docampo R, Li K, Liu YL, Oldfield E, Guo RT. Squalene synthase as a target for Chagas disease therapeutics. PLoS Pathog. 2014 May 1;10(5):e1004114. doi: 10.1371/journal.ppat.1004114., eCollection 2014 May. PMID:24789335 doi:http://dx.doi.org/10.1371/journal.ppat.1004114