The authors identified the role of the protein insig-1 in regulation of HMG-CoA reductase by degradation. This study described the relationship between ubiquitination, degradation, and the protein insig-1 in HMG-CoA reductase degradation.
In this study, the authors identified the specific amino acid of mammalian HMG-CoA reductase that is phosphorylated and mediates regulation of HMG-CoA reductase by reversible phosphorylation.
Eur J Biochem. A study that illustrated that plant HMG-CoA reductases are probably regulated by reversible phosphorylation. Ensembl Human Genome browser. Nucleic Acids Res. TreeTop - Phylogenetic tree prediction. A program for phylogenetic tree generation. National Center for Biotechnology Information. Download references. You can also search for this author in PubMed Google Scholar. Correspondence to Jon A Friesen. Reprints and Permissions. Friesen, J. Genome Biol 5, Download citation.
Published : 01 November Anyone you share the following link with will be able to read this content:. Sorry, a shareable link is not currently available for this article. Provided by the Springer Nature SharedIt content-sharing initiative. Skip to main content. Search all BMC articles Search. Download PDF. Summary The enzyme 3-hydroxymethylglutaryl coenzyme A HMG-CoA reductase catalyzes the conversion of HMG-CoA to mevalonate, a four-electron oxidoreduction that is the rate-limiting step in the synthesis of cholesterol and other isoprenoids.
Gene organization and evolutionary history The human hmgr gene that encodes the single human HMG-CoA reductase is located on chromosome 5, map location 5q Figure 1. Full size image. Figure 2. Table 1 Details of the sequences used for the phylogenetic tree in Figure 2 Full size table. Characteristic structural features The HMGRs of different organisms are multimers of a species-specific number of identical monomers.
Figure 3. This page, as it appeared on December 23, , was featured in this article in the journal Biochemistry and Molecular Biology Education. HMGR is a transmembrane protein, containing 8 domains, that is anchored in the membrane of the endoplasmic reticulum. Brown and Joseph L. HMGR is among the most highly regulated enzymes in the human body.
It catalyzes the formation of mevalonic acid, the committed step in the biosynthesis of sterols, most notably cholesterol. Despite the poor reputation cholesterol has in the media, it is a critical component of cellular membranes as it is required to establish proper membrane permeability and fluidity. The mevalonate pathway is also responsible for synthesis of the oxygen transporting heme found in red blood cells. As these methodologies continue to improve, they prove to be very powerful for the study of enzyme mechanisms in conjunction with protein crystallography.
Nevertheless, even the most current mechanistic proposal for HMGR remains incomplete due to limitations of the current computational methodologies. Thus, HMGR serves as a model for how the combination of increasingly sophisticated experimental and computational methods can elucidate very complex enzyme mechanisms.
Structures associated with Figures 11 and 13 in. Such files may be downloaded by article for research use if there is a public use license linked to the relevant article, that license may permit other uses.
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Cell Biol. Accelerated degradation of HMG CoA reductase mediated by binding of insig-1 to its sterol-sensing domain. Cell 11 , 25—33 Gp78, a membrane-anchored ubiquitin ligase, associates with Insig-1 and couples sterol-regulated ubiquitination to degradation of HMG CoA reductase.
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We thank Y. You can also search for this author in PubMed Google Scholar. Reprints and Permissions. Jiang, SY. Discovery of a potent HMG-CoA reductase degrader that eliminates statin-induced reductase accumulation and lowers cholesterol. Nat Commun 9, Download citation. Received : 12 July Accepted : 31 October
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