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| | '''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<ref>PMID:11008488</ref>. | | '''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<ref>PMID:11008488</ref>. |
| - | *'''Dehydrosqualene synthase''' of '''phytene synthase''' catalyzes the condensation of farnesyl diphosphate producing presqualene diphosphate<ref>PMID:21098670</ref>. | + | *'''Dehydrosqualene synthase''' or '''phytene synthase''' catalyzes the condensation of farnesyl diphosphate producing presqualene diphosphate<ref>PMID:21098670</ref>. |
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| | == Relevance == | | == Relevance == |
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| | ==3D structures of squalene synthase== | | ==3D structures of squalene synthase== |
| - | | + | [[Squalene synthase 3D structures]] |
| - | Updated on {{REVISIONDAY2}}-{{MONTHNAME|{{REVISIONMONTH}}}}-{{REVISIONYEAR}}
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| - | {{#tree:id=OrganizedByTopic|openlevels=0|
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| - | *Squalene synthase
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| - | **[[3vj8]], [[3vjb]] – hSQS – human<br />
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| - | **[[1ezf]] – hSQS (mutant) <br />
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| - | **[[4hd1]] – SQS – ''Alicyclobacillus acidocaldarius'' <br />
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| - | *Squalene synthase complexes
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| - | **[[3lee]] – hSQS + Mg + bisphosphonate inhibitor<br />
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| - | **[[3asx]], [[3q2z]], [[3q30]] – hSQS + Mg + PO4 + inhibitor<br />
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| - | **[[3vj9]], [[3vja]] – hSQS + Ni<br />
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| - | **[[3vjc]] – hSQS + Mg + PO4 + zaragozic acid<br />
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| - | **[[3v66]] – hSQS + PO4 + inhibitor<br />
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| - | **[[3wef]] – hSQS + FPP analog<br />
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| - | **[[3weg]] – hSQS + Mg + FPP analog<br />
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| - | **[[3weh]] – hSQS + Mg + presqualene pyrophosphate<br />
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| - | **[[3wei]] – hSQS (mutant) + Mn + presqualene pyrophosphate<br />
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| - | **[[3wej]], [[3wek]] – hSQS (mutant) + Mg + presqualene pyrophosphate<br />
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| - | **[[3wc9]] – hSQS (mutant) + farnesyl thiopyrophosphate<br />
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| - | **[[3wcd]] – hSQS (mutant) + phenoxy thiocyanate derivative<br />
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| - | **[[3wcf]], [[3wch]], [[3wci]], [[3wcl]] – hSQS (mutant) + imidazole phosphonate derivative<br />
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| - | **[[3wcj]] – hSQS (mutant) + pyrrolidine derivative<br />
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| - | **[[3wcm]] – hSQS (mutant) + pyridine derivative<br />
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| - | **[[3wsa]], [[3wsb]] – hSQS (mutant) + tuberculosis drug<br />
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| - | **[[3wef]], [[3weg]] – hSQS + FPP analog <br />
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| - | **[[3weh]] – hSQS + presqualene pyrophosphate <br />
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| - | **[[3wei]], [[3wej]], [[3wek]] – hSQS (mutant) + presqualene pyrophosphate <br />
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| - | **[[3wca]], [[3wcb]], [[3wcc]], [[3wce]], [[3wcg]] – SQS (mutant) + FPP analog – ''Trypanosoma cruzi''<br />
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| - | **[[7wgi]] – AfSQS + PO4 + indole – ''Aspergillus flavus''<br />
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| - | **[[7wgh]] – AfSQS (mutant) + POP + PO4 +farnesyl thiopyrophosphate<br />
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| - | *Dehydrosqualene synthase (DSQS)
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| - | **[[3vjd]], [[2zco]] – SaDSQS – ''Staphylococcus aureus'' <br />
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| - | **[[3nri]] – SaDSQS + dehydrosqualene <br />
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| - | **[[3npr]], [[3adz]] – SaSQS + presqualene pyrophosphate <br />
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| - | **[[3lgz]] – SaSQS (mutant) + presqualene pyrophosphate <br />
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| - | **[[3vje]] – SaDSQS (mutant) + zaragozic acid <br />
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| - | **[[3ae0]] – SaDSQS + geranylgeranyl + thiopyrophosphate <br />
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| - | **[[3w7f]], [[5yis]] – SaDSQS + farnesyl + thiopyrophosphate <br />
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| - | **[[3acw]], [[3acx]], [[3acy]], [[3tfv]], [[3tfn]], [[3tfp]], [[4f6v]], [[4f6x]], [[2zcs]], [[2zcq]], [[2zy1]], [[2zcr]], [[4e9z]], [[4e9u]], [[4ea0]], [[4ea1]], [[4ea2]] – SaDSQS + inhibitor<br />
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| - | }}
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| | == References == | | == References == |
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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 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 [4]. Water molecules are shown as red spheres. .
3D structures of squalene synthase
Squalene synthase 3D structures
References
- ↑ 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:http://dx.doi.org/10.1371/journal.ppat.1004114
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