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| The <scene name='59/591996/Cv/6'>active site of SQS contains a substrate analog</scene><ref>PMID:24789335</ref>. Water molecules are shown as red spheres. | | The <scene name='59/591996/Cv/6'>active site of SQS contains a substrate analog</scene><ref>PMID:24789335</ref>. Water molecules are shown as red spheres. <scene name='59/591996/Cv/7'>Mg coordination site</scene>. |
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Revision as of 13:57, 23 November 2020
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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 of 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.
- ↑ Tansey TR, Shechter I. Squalene synthase: structure and regulation. Prog Nucleic Acid Res Mol Biol. 2001;65:157-95. PMID:11008488
- ↑ 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
- ↑ 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
- ↑ 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:https://dx.doi.org/10.1371/journal.ppat.1004114
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3D structures of squalene synthase
Updated on 23-November-2020
{"openlevels":0}
- Squalene synthase
- 3vj8, 3vjb – hSQS – human
- 1ezf – hSQS (mutant)
- 4hd1 – SQS – Alicyclobacillus acidocaldarius
- Squalene synthase complexes
- 3lee – hSQS + Mg + bisphosphonate inhibitor
- 3asx, 3q2z, 3q30 – hSQS + Mg + PO4 + inhibitor
- 3vj9, 3vja – hSQS + Ni
- 3vjc – hSQS + Mg + PO4 + zaragozic acid
- 3v66 – hSQS + PO4 + inhibitor
- 3wef – hSQS + FPP analog
- 3weg – hSQS + Mg + FPP analog
- 3weh – hSQS + Mg + presqualene pyrophosphate
- 3wei – hSQS (mutant) + Mn + presqualene pyrophosphate
- 3wej, 3wek – hSQS (mutant) + Mg + presqualene pyrophosphate
- 3wc9 – hSQS (mutant) + farnesyl thiopyrophosphate
- 3wcd – hSQS (mutant) + phenoxy thiocyanate derivative
- 3wcf, 3wch, 3wci, 3wcl – hSQS (mutant) + imidazole phosphonate derivative
- 3wcj – hSQS (mutant) + pyrrolidine derivative
- 3wcm – hSQS (mutant) + pyridine derivative
- 3wsa, 3wsb – hSQS (mutant) + tuberculosis drug
- 3wef, 3weg – hSQS + FPP analog
- 3weh – hSQS + presqualene pyrophosphate
- 3wei, 3wej, 3wek – hSQS (mutant) + presqualene pyrophosphate
- 3wca, 3wcb, 3wcc, 3wce, 3wcg – SQS (mutant) + FPP analog – Trypanosoma cruzi
- Dehydrosqualene synthase (DSQS)
- 3vjd, 2zco – SaDSQS – Staphylococcus aureus
- 3nri – SaDSQS + dehydrosqualene
- 3npr, 3adz – SaSQS + presqualene pyrophosphate
- 3lgz – SaSQS (mutant) + presqualene pyrophosphate
- 3vje – SaDSQS (mutant) + zaragozic acid
- 3ae0 – SaDSQS + geranylgeranyl + thiopyrophosphate
- 3w7f, 5yis – SaDSQS + farnesyl + thiopyrophosphate
- 3acw, 3acx, 3acy, 3tfv, 3tfn, 3tfp, 4f6v, 4f6x, 2zcs, 2zcq, 2zy1, 2zcr, 4e9z, 4e9u, 4ea0, 4ea1, 4ea2 – SaDSQS + inhibitor
References
