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Literature summary extracted from

  • Liu, C.I.; Jeng, W.Y.; Chang, W.J.; Ko, T.P.; Wang, A.H.
    Binding modes of zaragozic acid A to human squalene synthase and staphylococcal dehydrosqualene synthase (2012), J. Biol. Chem., 287, 18750-18757.
    View publication on PubMedView publication on EuropePMC

Application

EC Number Application Comment Organism
2.5.1.21 medicine squalene synthase is a potential target for antilipogenic and antiinfective therapies Homo sapiens

Cloned(Commentary)

EC Number Cloned (Comment) Organism
2.5.1.21 gene fragment SQS(31-370) as N-terminally His6-tagged protein containing a thrombin cleavage site in Escherichia coli strain BL21(DE3) Homo sapiens

Crystallization (Commentary)

EC Number Crystallization (Comment) Organism
2.5.1.21 purified recombinant truncated detagged SQS(31-370) in complex with inhibitor zaragozic acid A, vapour diffusion, mixing an equal volume of protein solution containing 15 mg/ml protein with precipitating solution containing 20% PEG2K-MME, 0.01 M NiCl2, 0.1 M Tris, pH 8.5, 1.4 M sodium citrate tribasic dehydrate, 0.1 M Na-HEPES, pH 7.5, 2 M K2HPO4/NaH2HPO4, pH 6.5, room temperature, X-ray diffraction structure determination and analysis, molecular replacement Homo sapiens
2.5.1.96 mutant Y248A in complex with zaragozic acid A, to 2.1 A resolution. Crystals grow in the hexagonal space group P3121 and contain two molecules per asymmetric unit. The active site of each protein is occupied by a molecule zazgozic acid A. The highly oxygenated core structure contacts residues 19SKSF22. The C-1 lipophilic tail extends into the narrow pocket which is lined with hydrophobic residues that help to stabilize the interaction with the isoprenoid moiety of the donor farnesyl diphosphate, S1 site.The side chains of Phe22 and Phe26 are moved toward the bottom of the active site, and the orientation of the Tyr41 side chain provides sufficient space for stabilization of the zaragozic acid A C-1 unit in the S1 site Staphylococcus aureus

Protein Variants

EC Number Protein Variants Comment Organism
2.5.1.96 Y248A crystallization data of complex with zaragozic acid A Staphylococcus aureus

Inhibitors

EC Number Inhibitors Comment Organism Structure
2.5.1.21 zaragozic acid A enzyme binding induces a local conformational change in the substrate binding site, and its C-6 acyl group also extends over to the cofactor binding cavity, enzyme-inhibitor binding structure and thermodynamics, detailed overview Homo sapiens
2.5.1.96 zaragozic acid A crystallization data of complex Staphylococcus aureus

Localization

EC Number Localization Comment Organism GeneOntology No. Textmining
2.5.1.21 endoplasmic reticulum
-
 Homo sapiens 5783
-

Organism

EC Number Organism UniProt Comment Textmining
2.5.1.21 Homo sapiens
-
-
-
2.5.1.96 Staphylococcus aureus
-
-
-

Purification (Commentary)

EC Number Purification (Comment) Organism
2.5.1.21 recombinant truncated N-terminally His6-tagged SQS(31-370) from Escherichia coli strain BL21(DE3), the tag is cleaved off by thrombin Homo sapiens

Reaction

EC Number Reaction Comment Organism Reaction ID
2.5.1.21 2 (2E,6E)-farnesyl diphosphate + NAD(P)H + H+ = squalene + 2 diphosphate + NAD(P)+ overall reaction, reaction mechanism, overview Homo sapiens
a

Substrates and Products (Substrate)

EC Number Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
2.5.1.21 2 (2E,6E)-farnesyl diphosphate
-
 Homo sapiens diphosphate + presqualene diphosphate
-
 ?
2.5.1.21 2 (2E,6E)-farnesyl diphosphate + NADPH + H+ overall reaction Homo sapiens squalene + 2 diphosphate + NADP+
-
 ?
2.5.1.21 presqualene diphosphate + NADPH + H+
-
 Homo sapiens squalene + diphosphate + NADP+
-
 ?

Synonyms

EC Number Synonyms Comment Organism
2.5.1.21 SQS
-
 Homo sapiens

Cofactor

EC Number Cofactor Comment Organism Structure
2.5.1.21 NADPH region IV of SQS may constitute a functional NADPH binding site Homo sapiens

General Information

EC Number General Information Comment Organism
2.5.1.21 malfunction modifications in region IV prevents SQS from undergoing the second half-reaction, indicating that this region may reasonably constitute a functional NADPH binding site Homo sapiens
2.5.1.21 metabolism squalene synthase catalyzes the committed step of sterol synthesis Homo sapiens