Literature summary for 2.5.1.21 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.

Application

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

Cloned(Commentary)

Cloned (Comment)	Organism
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)

Crystallization (Comment)	Organism
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

Crystallization (Comment)

Organism

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

Inhibitors

Inhibitors	Comment	Organism	Structure
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

Localization

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

Organism

Organism	UniProt	Comment	Textmining
Homo sapiens	-	-	-

Purification (Commentary)

Purification (Comment)	Organism
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

Reaction	Comment	Organism	Reaction ID
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)

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

Synonyms

Synonyms	Comment	Organism
SQS	-	Homo sapiens

Cofactor

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

General Information

General Information	Comment	Organism
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
metabolism	squalene synthase catalyzes the committed step of sterol synthesis	Homo sapiens