2.5.1.21: squalene synthase
This is an abbreviated version!
For detailed information about squalene synthase, go to the full flat file.
Word Map on EC 2.5.1.21
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2.5.1.21
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farnesylation
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cholesterol
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prenylation
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sterol
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ftase
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mevalonate
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geranylgeranylation
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isoprenoids
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leukemia
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geranylgeranyltransferase
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pyrophosphate
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tipifarnib
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hmg-coa
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statin
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h-ras
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peptidomimetic
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epoxidase
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prenyltransferase
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dolichols
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rhob
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isoprenylation
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triterpene
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farnesol
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3-hydroxy-3-methylglutaryl
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lamins
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ergosterol
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cholesterol-lowering
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hmgcr
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prelamin
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p21ras
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lovastatin
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hutchinson-gilford
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lanosterol
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manumycin
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triterpenoids
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synthesis
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progerin
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farnesylpyrophosphate
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cis-prenyltransferase
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drug development
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oxidosqualene
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ras-transformed
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medicine
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ras-dependent
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nonsterols
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ras-mediated
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withanolides
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srebp-2
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ganoderic
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agriculture
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geranylgeraniol
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industry
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cycloartenol
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non-thiol
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2,3-oxidosqualene
- 2.5.1.21
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farnesylation
- cholesterol
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prenylation
- sterol
- ftase
- mevalonate
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geranylgeranylation
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isoprenoids
- leukemia
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geranylgeranyltransferase
- pyrophosphate
- tipifarnib
- hmg-coa
- statin
- h-ras
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peptidomimetic
-
epoxidase
- prenyltransferase
- dolichols
- rhob
-
isoprenylation
-
triterpene
- farnesol
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3-hydroxy-3-methylglutaryl
- lamins
- ergosterol
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cholesterol-lowering
- hmgcr
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prelamin
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p21ras
- lovastatin
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hutchinson-gilford
- lanosterol
- manumycin
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triterpenoids
- synthesis
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progerin
-
farnesylpyrophosphate
- cis-prenyltransferase
- drug development
- oxidosqualene
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ras-transformed
- medicine
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ras-dependent
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nonsterols
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ras-mediated
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withanolides
- srebp-2
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ganoderic
- agriculture
- geranylgeraniol
- industry
- cycloartenol
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non-thiol
- 2,3-oxidosqualene
Reaction
2 (2E,6E)-farnesyl diphosphate + + = + 2 diphosphate +
Synonyms
BbSS, BSS, CrSQS, dt-ySQase, Erg9, EtSS, farnesyl-diphosphate farnesyltransferase, farnesyl-diphosphate:farnesyldiphosphate farnesyltransferase, farnesyldiphosphate farnesyltransferase 1, farnesyldiphosphate:farnesyldiphosphate farnesyltransferase, farnesyltransferase, FDFT1, hSQS, presqualene synthase, presqualene-diphosphate synthase, SgSQS, SQase, SQS, SQS1, SQS2, squalene synthase, squalene synthase 1, squalene synthase 2, squalene synthetase, SS1, SSase, SSN, synthase, squalene, TkSQS1, TkSQS2
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General Information
General Information on EC 2.5.1.21 - squalene synthase
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evolution
malfunction
metabolism
physiological function
additional information
phylogenetic analysis of SQS enzymes in plants shows highly similar conserved pattern including 77DTVED81 and 213DYLED217 motifs, which are rich in aspartic acids involved in FPP binding
evolution
phylogenetic analysis of SQS enzymes in plants shows highly similar conserved pattern including 77DTVED81 and 213DYLED217 motifs, which are rich in aspartic acids involved in FPP binding
evolution
the enzyme belongs to the isoprenoid biosynthesis enzymes class 1 superfamily
evolution
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the enzyme belongs to the isoprenoid biosynthesis enzymes class 1 superfamily
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Inhibition of squalene synthase leads directly to a reduction in cholesterol biosynthesis and thus to a fall in plasma cholesterol levels. Plasma LDL-cholesterol and triglycerides are lowered by squalene synthase inhibitors
malfunction
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modifications in region IV prevents SQS from undergoing the second half-reaction, indicating that this region may reasonably constitute a functional NADPH binding site
malfunction
enzyme overexpression in transgenic Withania somnifera plants affects the shoot elongation and multiplication, phenotype, overview
malfunction
the SQS inhibitors YM-53601 and zaragozic acid A decrease hepatitis C virus RNA, protein, and progeny production in HCV-infected cells without affecting cell viability, using the HCV JFH-1 strain and human hepatoma Huh-7.5.1-derived cells. siRNA-mediated knockdown of SQS leads to significantly reduced HCV production, confirming the enzyme acts as an antiviral target. A metabolic labeling study demonstrates that enzyme inhibitor YM-53601 suppresses the biosynthesis of cholesterol and cholesteryl esters at antiviral concentrations
metabolism
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squalene synthase catalyzes the conversion of farnesyl pyrophosphate into squalene by reductive condensation. This is a crucial step in cholesterol biosynthesis, squalene serves as the exclusive precursor for cholesterol
metabolism
squalene synthase catalyzes the first enzymatic step of the central isoprenoid pathway in sterol and triterpenoid biosynthesis
metabolism
squalene synthase is a key enzyme in the regulation of isoprenoid biosynthesis and is important in the withanolides biosynthesis pathway, overview
metabolism
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squalene synthase is a key enzyme involved in antifungal steroidal glycoalkaloids biosynthesis. Steroidal glycoalkaloids are a family of nitrogenous secondary metabolites acting as phytoalexins, e.g. gamma-solamargine and its aglycone solasodine from Solanum nigrum inhibiting hyphae formation of Fusarium oxysporum
metabolism
squalene synthase is a major enzyme in the sterol biosynthetic pathway
metabolism
squalene synthase is the key enzyme of saponin biosynthesis pathway
metabolism
enzyme SQS operates at a branch point of the withanolide biosynthetic pathway regulating the metabolic flux and catalyzes the first committed step leading to the synthesis of different withanolides
metabolism
four major steps - substrate binding, condensation, intermediate formation and translocation - of the ordered sequential mechanisms involved in the 1'-1 isoprenoid biosynthetic pathway
metabolism
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squalene synthase catalyzes the first committed step in sterol biosynthesis
metabolism
squalene synthase catalyzes the first committed step in sterol biosynthesis
metabolism
squalene synthase catalyzes the first committed step in sterol biosynthesis
metabolism
squalene synthase catalyzes the first committed step in sterol biosynthesis, role of squalene synthase in the ergosterol biosynthetic pathway of budding yeast, overview
metabolism
Thermosynechococcus vestitus
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squalene synthase catalyzes the first step of sterol/hopanoid biosynthesis in the organism
metabolism
squalene synthase catalyzes the first step of sterol/hopanoid biosynthesis in the organism
metabolism
squalene synthase catalyzes the first step of sterol/hopanoid biosynthesis in the organism
metabolism
the enzyme catalyzes the first dedicated step in the biosynthesis of sterols and other triterpenoids
metabolism
the enzyme catalyzes the first dedicated step in the biosynthesis of sterols and other triterpenoids
metabolism
the enzyme is a key enzyme in the isoprenoid biosynthesis
metabolism
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the enzyme is involved in squalene synthesis and sterol metabolism
metabolism
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squalene synthase catalyzes the first enzymatic step from the central isoprenoid pathway toward sterol and triterpenoid biosynthesis
metabolism
the enzyme catalyzes a key steps in the biosynthesis of cyclic terpenoids
metabolism
the enzyme is involved in celastrol biosynthesis
metabolism
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the enzyme is a key enzyme in the isoprenoid biosynthesis
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metabolism
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squalene synthase is a major enzyme in the sterol biosynthetic pathway
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physiological function
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influence on regulation of cholesterol metabolism
physiological function
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influence on regulation of cholesterol metabolism
physiological function
squalene synthase catalyses an unusual head-to-head reductive dimerization of two molecules of farnesyl-pyrophosphate in a two-step reaction to form squalene
physiological function
squalene synthase functions as a key regulator in channeling the carbon flux into both the primary and secondary metabolite branches, and squalene synthase may play a regulatory role in directing triterpene intermediates and sterol pathways
physiological function
enzyme SQS plays an important role in regulating isoprenoid biosynthesis in eukaryotes
physiological function
SQS play an important regulatory role in phytosterol biosynthetic pathway
physiological function
Thermosynechococcus vestitus
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squalene is biosynthesized via the head-to-head condensation of two molecules of farnesyl diphosphate, which is catalyzed by the single enzyme squalene synthase. Squalene is a precursor of thousands of bioactive triterpenoids
physiological function
squalene is biosynthesized via the head-to-head condensation of two molecules of farnesyl diphosphate, which is catalyzed by the single enzyme squalene synthase. Squalene is a precursor of thousands of bioactive triterpenoids
physiological function
squalene synthase is the rate-limiting enzyme located at the downstream of cholesterol synthesis pathway
physiological function
the catalytic domain performs the head-to-head dimerization of two molecules of farnesyl diphosphate to form squalene, a 30 carbon isoprenoid oxidized by squalene monooxygenase (Erg1) and cyclized by lanosterol synthase
physiological function
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the enzyme is involved in squalene synthesis and sterol metabolism
physiological function
the enzyme squalene synthase catalyzes the first committed step in sterol biosynthesis by condensing two molecules of farnesyl diphosphate into squalene in two reaction steps
physiological function
the enzyme squalene synthase catalyzes the first committed step in sterol biosynthesis by condensing two molecules of farnesyl diphosphate into squalene in two reaction steps
physiological function
squalene and botryococcene are branched-chain, triterpene compounds that arise from the head-tohead condensation of two molecules of farnesyl diphosphate to yield 1'-1 and 1'-3 linkages, respectively
physiological function
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squalene synthase catalyses an unusual head-to-head reductive dimerization of two molecules of farnesyl-pyrophosphate in a two-step reaction to form squalene
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enzyme overexpression leads a significant 4fold enhancement in squalene synthase activity and 2.5fold enhancement in withanolide A content, transformed cell suspension cultures also produce withaferin A, which is absent in the non-transformed cell cultures
additional information
methyl jasmonate, abscisic acid, and ethephon induce the accumulation of BfSS1 mRNA, overexpression of the BfSS1 gene in the sense orientation in Bupleurum falcatum increases the mRNA accumulation of downstream genes such as squalene epoxidase and cycloartenol synthase but decreases the mRNA levels of beta-amyrin synthase, a triterpene synthase mRNA. Methyljasmonate treatment of transgenic roots overexpressing BfSS1 in the sense orientation fails to stimulate beta-amyrin synthase mRNA accumulation but still enhances saikosaponin and phytosterol production
additional information
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methyl jasmonate, abscisic acid, and ethephon induce the accumulation of BfSS1 mRNA, overexpression of the BfSS1 gene in the sense orientation in Bupleurum falcatum increases the mRNA accumulation of downstream genes such as squalene epoxidase and cycloartenol synthase but decreases the mRNA levels of beta-amyrin synthase, a triterpene synthase mRNA. Methyljasmonate treatment of transgenic roots overexpressing BfSS1 in the sense orientation fails to stimulate beta-amyrin synthase mRNA accumulation but still enhances saikosaponin and phytosterol production
additional information
the catalytic site is composed of the large central cavity formed by antiparallel alpha helices with two aspartate rich regions (DXXXD) on opposite walls, these residues are considered to play roles in binding of prenyl phosphates by binding Mg2+ ions
additional information
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the catalytic site is composed of the large central cavity formed by antiparallel alpha helices with two aspartate rich regions (DXXXD) on opposite walls, these residues are considered to play roles in binding of prenyl phosphates by binding Mg2+ ions
additional information
the substrate binding site is present at the core region of the enzyme structure. The predicted active site involves Phe 204, Leu 205, Gln 206, Thr 208, Asn 209, Ala 293, and Leu 297. The aspartate side chains are involved in binding multiple Mg2+ ions that stabilize binding of diphosphate groups in the substrate.
additional information
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the substrate binding site is present at the core region of the enzyme structure. The predicted active site involves Phe 204, Leu 205, Gln 206, Thr 208, Asn 209, Ala 293, and Leu 297. The aspartate side chains are involved in binding multiple Mg2+ ions that stabilize binding of diphosphate groups in the substrate.
additional information
determination and analysis of human SQS and its mutants in complex with several substrate analogues and intermediates coordinated with Mg2+ or Mn2+, SQS active analysis, overview
additional information
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determination and analysis of human SQS and its mutants in complex with several substrate analogues and intermediates coordinated with Mg2+ or Mn2+, SQS active analysis, overview
additional information
functional analyses of the enzyme's two DXXD(E)D motifs and the highly conserved aromatic amino acid residues, kinetic analysis and reaction mechanism, overview. The potential active-site residues 58DXX61E62D (S1 site) and 213DXX216D217D (S2 site) are assumed to be involved in the binding of the substrate farnesyl diphosphate through the Mg2+ ion. The S1 site and the two basic residues R55 and K212 are responsible for the binding of farnesyl diphosphate
additional information
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functional analyses of the enzyme's two DXXD(E)D motifs and the highly conserved aromatic amino acid residues, kinetic analysis and reaction mechanism, overview. The potential active-site residues 58DXX61E62D (S1 site) and 213DXX216D217D (S2 site) are assumed to be involved in the binding of the substrate farnesyl diphosphate through the Mg2+ ion. The S1 site and the two basic residues R55 and K212 are responsible for the binding of farnesyl diphosphate
additional information
homology modelling of SQS enzyme of Withania somnifera for the prediction of three-dimensional structure, molecular docking study of considered substrates, overview
additional information
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homology modelling of SQS enzyme of Withania somnifera for the prediction of three-dimensional structure, molecular docking study of considered substrates, overview
additional information
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squalene does not accumulate significantly in CrSQS-overexpressing cells, although conversion of farnesyl diphosphate to squalene is enhanced by overexpression of enzyme CrSQS
additional information
structure homology modelling using the crystal structure of human squalene synthase, PDB ID 1EZFB, as template, overview
additional information
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structure homology modelling using the crystal structure of human squalene synthase, PDB ID 1EZFB, as template, overview
additional information
the hinge domain plays an essential functional role, such as assembly of ergosterol multi-enzymecomplexes in fungi
additional information
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the hinge domain plays an essential functional role, such as assembly of ergosterol multi-enzymecomplexes in fungi
additional information
proposed catalytic cascades for the enzyme-mediated biosynthesis of squalene and botryococcene, and molecular modeling of Botryococcus braunii botryococcene and squalene synthase enzymes, overview. Substrate docking and molecular modeling
additional information
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proposed catalytic cascades for the enzyme-mediated biosynthesis of squalene and botryococcene, and molecular modeling of Botryococcus braunii botryococcene and squalene synthase enzymes, overview. Substrate docking and molecular modeling
additional information
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structure homology modelling using the crystal structure of human squalene synthase, PDB ID 1EZFB, as template, overview
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