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| **[[3wei]], [[3wej]], [[3wek]] – hSQS (mutant) + presqualene pyrophosphate <br /> | | **[[3wei]], [[3wej]], [[3wek]] – hSQS (mutant) + presqualene pyrophosphate <br /> |
| **[[3wca]], [[3wcb]], [[3wcc]], [[3wce]], [[3wcg]] – SQS (mutant) + FPP analog – ''Trypanosoma cruzi''<br /> | | **[[3wca]], [[3wcb]], [[3wcc]], [[3wce]], [[3wcg]] – SQS (mutant) + FPP analog – ''Trypanosoma cruzi''<br /> |
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| | *Dehydrosqualene synthase (DSQS) |
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| | **[[3vjd]], [[2zco]] – SaDSQS – ''Staphylococcus aureus'' <br /> |
| | **[[3nri]] – SaDSQS + dehydrosqualene <br /> |
| | **[[3npr]], [[3adz]] – SaSQS + presqualene pyrophosphate <br /> |
| | **[[3lgz]] – SaSQS (mutant) + presqualene pyrophosphate <br /> |
| | **[[3vje]] – SaDSQS (mutant) + zaragozic acid <br /> |
| | **[[3ae0]] – SaDSQS + geranylgeranyl + thiopyrophosphate <br /> |
| | **[[3w7f]], [[5yis]] – SaDSQS + farnesyl + thiopyrophosphate <br /> |
| | **[[3acw]], [[3acx]], [[3acy]], [[3tfv]], [[3tfn]], [[3tfp]], [[4f6v]], [[4f6x]], [[2zcs]], [[2zcq]], [[2zy1]], [[2zcr]], [[4e9z]], [[4e9u]], [[4ea0]], [[4ea1]], [[4ea2]] – SaDSQS + inhibitor<br /> |
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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].
Relevance
SQS inhibitors are tested for antihyperlipidemic and antiatherosclerotic agents[2].
Structural highlights
The active site of SQS contains a substrate analog[3]. Water molecules are shown as red spheres.
- ↑ Tansey TR, Shechter I. Squalene synthase: structure and regulation. Prog Nucleic Acid Res Mol Biol. 2001;65:157-95. PMID:11008488
- ↑ 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 11-November-2020
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- 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