Sandbox Reserved 991
From Proteopedia
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[[Image:Lanosterol synthase.jpg | thumb]] | [[Image:Lanosterol synthase.jpg | thumb]] | ||
| - | Since lanosterol synthase is involved in cholesterol biosynthesis, there is clinical relevance in using lanosterol synthase inhibitors to develop cholesterol lowering drugs. These drugs could then potentially be used in conjunction with | + | Since lanosterol synthase is involved in cholesterol biosynthesis, there is clinical relevance in using lanosterol synthase inhibitors to develop cholesterol lowering drugs. These drugs could then potentially be used in conjunction with statins. |
Revision as of 07:13, 24 February 2015
| This Sandbox is Reserved from 20/01/2015, through 30/04/2016 for use in the course "CHM 463" taught by Mary Karpen at the Grand Valley State University. This reservation includes Sandbox Reserved 987 through Sandbox Reserved 996. |
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This is a default text for your page '. Click above on edit this page' to modify. Be careful with the < and > signs. You may include any references to papers as in: the use of JSmol in Proteopedia [1] or to the article describing Jmol [2] to the rescue.
Contents |
Introduction
Lanosterol synthase is an important oxidosqualene cyclase enzyme in the cholesterol biosynthesis pathway. It converts 2,3-Oxidosqualene to a protosterol cation and then to Lanosterol. Lanosterol is a crucial four-ringed precursor to cholesterol.
Since lanosterol synthase is involved in cholesterol biosynthesis, there is clinical relevance in using lanosterol synthase inhibitors to develop cholesterol lowering drugs. These drugs could then potentially be used in conjunction with statins.
Mechanism
Acetyl-CoA is converted to six five carbon long isoprene units. These isoprene units then affix to generate a long 30 carbon molecule called squalene. Squalene will ultimately cyclizes to form the four-ring arrangement of cholesterol.
Structure
Mutagenic analysis has determined that there are three residues vital to protein function: .[3] The opening of the epoxide ring of 2,3-oxidosqualene requires protonation by the enzyme. The proton donor is the aspartic acid residue D455. Conversely, in the second step of the reaction, a proton is removed from C9 and is accepted by the histidine residue H232.
Function
The enzyme oxidosqualene cyclase carries out the most complex phase of cholesterol synthesis. It takes a lengthy skinny carbon chain, oxidosqualene, and folds it to create a cyclic compound composed of four connected rings.
Cholesterol Biosynthesis
Disease
Structural highlights
This is a sample scene created with SAT to by Group, and another to make of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes.
References
- ↑ Hanson, R. M., Prilusky, J., Renjian, Z., Nakane, T. and Sussman, J. L. (2013), JSmol and the Next-Generation Web-Based Representation of 3D Molecular Structure as Applied to Proteopedia. Isr. J. Chem., 53:207-216. doi:http://dx.doi.org/10.1002/ijch.201300024
- ↑ Herraez A. Biomolecules in the computer: Jmol to the rescue. Biochem Mol Biol Educ. 2006 Jul;34(4):255-61. doi: 10.1002/bmb.2006.494034042644. PMID:21638687 doi:10.1002/bmb.2006.494034042644
- ↑ Corey EJ, Cheng CH, Baker CH, Matsuda SPT, Li D, Song X (February 1997). "Studies on the Substrate Binding Segments and Catalytic Action of Lanosterol Synthase. Affinity Labeling with Carbocations Derived from Mechanism-Based Analogs of 2, 3-Oxidosqualene and Site-Directed Mutagenesis Probes". J. Am. Chem. Soc. 119 (6): 1289–96.
