Conservation between Human and Fungal Squalene Synthetases: Similarities in Structure, Function, and Regulation
| Autor: | Bernadette Kienzle, Constance Smith-Monroy, Y H Tsay, Gordon William Robinson, Richard W. Bishop |
|---|---|
| Rok vydání: | 1993 |
| Předmět: |
Adult
Farnesyltransferase Molecular Sequence Data Restriction Mapping Saccharomyces cerevisiae Polymerase Chain Reaction Ligases Squalene chemistry.chemical_compound Prenylation Sequence Homology Nucleic Acid Schizosaccharomyces Escherichia coli Humans Amino Acid Sequence Cloning Molecular Molecular Biology Gene Library chemistry.chemical_classification Farnesyl-diphosphate farnesyltransferase Alkyl and Aryl Transferases Base Sequence Sequence Homology Amino Acid biology DNA Cell Biology biology.organism_classification Bacteriophage lambda Biological Evolution Recombinant Proteins Farnesyl-Diphosphate Farnesyltransferase Enzyme Liver Oligodeoxyribonucleotides Biochemistry chemistry Geranylgeranyl-Diphosphate Geranylgeranyltransferase Schizosaccharomyces pombe biology.protein Research Article HeLa Cells Plasmids |
| Zdroj: | Molecular and Cellular Biology. 13:2706-2717 |
| ISSN: | 1098-5549 |
| Popis: | Squalene synthetase (farnesyl diphosphate:farnesyl diphosphate farnesyltransferase; EC 2.5.1.21) is thought to represent a major control point of isoprene and sterol biosynthesis in eukaryotes. We demonstrate structural and functional conservation between the enzymes from humans, a budding yeast (Saccharomyces cerevisiae), and a fission yeast (Schizosaccharomyces pombe). The amino acid sequences of the human and S. pombe proteins deduced from cloned cDNAs were compared to those of the known S. cerevisiae protein. All are predicted to encode C-terminal membrane-spanning proteins of approximately 50 kDa with similar hydropathy profiles. Extensive sequence conservation exists in regions of the enzyme proposed to interact with its prenyl substrates (i.e., two farnesyl diphosphate molecules). Many of the highly conserved regions are also present in phytoene and prephytoene diphosphate synthetases, enzymes which catalyze prenyl substrate condensation reactions analogous to that of squalene synthetase. Expression of cDNA clones encoding S. pombe or hybrid human-S. cerevisiae squalene synthetases reversed the ergosterol requirement of S. cerevisiae cells bearing ERG9 gene disruptions, showing that these enzymes can functionally replace the S. cerevisiae enzyme. Inhibition of sterol synthesis in S. cerevisiae and S. pombe cells or in cultured human fibroblasts by treatment with the 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor lovastatin resulted in elevated levels of squalene synthetase mRNA in all three cell types. |
| Databáze: | OpenAIRE |
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