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Squalene synthase
From Proteopedia
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| - | <StructureSection load=' | + | <StructureSection load='3wca' size='350' side='right' caption='Structure of SQS complex with FPP analog and Mg+2 ions (green) (PDB code [[3wca]]).' scene='59/591996/Cv/1'> |
== Function == | == 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. | + | '''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>. |
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== Relevance == | == Relevance == | ||
| + | SQS inhibitors are tested for antihyperlipidemic and antiatherosclerotic agents<ref>PMID:21864285</ref>. | ||
== Structural highlights == | == Structural highlights == | ||
| + | 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>. | ||
| + | </StructureSection> | ||
==3D structures of squalene synthase== | ==3D structures of squalene synthase== | ||
Updated on {{REVISIONDAY2}}-{{MONTHNAME|{{REVISIONMONTH}}}}-{{REVISIONYEAR}} | Updated on {{REVISIONDAY2}}-{{MONTHNAME|{{REVISIONMONTH}}}}-{{REVISIONYEAR}} | ||
| + | {{#tree:id=OrganizedByTopic|openlevels=0| | ||
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| + | *Squalene synthase | ||
| + | |||
| + | **[[3vj8]], [[3vjb]] – hSQS – human<br /> | ||
| + | **[[1ezf]] – hSQS (mutant) <br /> | ||
| + | **[[4hd1]] – SQS – ''Alicyclobacillus acidocaldarius'' <br /> | ||
| - | + | *Squalene synthase complexes | |
| - | + | ||
| - | ''' | + | **[[3lee]] – hSQS + Mg + bisphosphonate inhibitor<br /> |
| + | **[[3asx]], [[3q2z]], [[3q30]] – hSQS + Mg + PO4 + inhibitor<br /> | ||
| + | **[[3vj9]], [[3vja]] – hSQS + Ni<br /> | ||
| + | **[[3vjc]] – hSQS + Mg + PO4 + zaragozic acid<br /> | ||
| + | **[[3v66]] – hSQS + PO4 + inhibitor<br /> | ||
| + | **[[3wef]] – hSQS + FPP analog<br /> | ||
| + | **[[3weg]] – hSQS + Mg + FPP analog<br /> | ||
| + | **[[3weh]] – hSQS + Mg + presqualene pyrophosphate<br /> | ||
| + | **[[3wei]] – hSQS (mutant) + Mn + presqualene pyrophosphate<br /> | ||
| + | **[[3wej]], [[3wek]] – hSQS (mutant) + Mg + presqualene pyrophosphate<br /> | ||
| + | **[[3wc9]] – hSQS (mutant) + farnesyl thiopyrophosphate<br /> | ||
| + | **[[3wcd]] – hSQS (mutant) + phenoxy thiocyanate derivative<br /> | ||
| + | **[[3wcf]], [[3wch]], [[3wci]], [[3wcl]] – hSQS (mutant) + imidazole phosphonate derivative<br /> | ||
| + | **[[3wcj]] – hSQS (mutant) + pyrrolidine derivative<br /> | ||
| + | **[[3wcm]] – hSQS (mutant) + pyridine derivative<br /> | ||
| + | **[[3wsa]], [[3wsb]] – hSQS (mutant) + tuberculosis drug<br /> | ||
| + | **[[3wef]], [[3weg]] – hSQS + FPP analog <br /> | ||
| + | **[[3weh]] – hSQS + presqualene pyrophosphate <br /> | ||
| + | **[[3wei]], [[3wej]], [[3wek]] – hSQS (mutant) + presqualene pyrophosphate <br /> | ||
| + | **[[3wca]], [[3wcb]], [[3wcc]], [[3wce]], [[3wcg]] – SQS (mutant) + FPP analog – ''Trypanosoma cruzi''<br /> | ||
| + | **[[7wgi]] – AfSQS + PO4 + indole – ''Aspergillus flavus''<br /> | ||
| + | **[[7wgh]] – AfSQS (mutant) + POP + PO4 +farnesyl thiopyrophosphate<br /> | ||
| - | [[ | + | *Dehydrosqualene synthase (DSQS) |
| - | [[ | + | |
| - | [[ | + | **[[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 /> |
| + | }} | ||
== References == | == References == | ||
Current revision
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3D structures of squalene synthase
Updated on 04-December-2023
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
