User:Lisa M. Leone/Sandbox 1
From Proteopedia
This is my sandbox
Add to Taxol discussion - stabilization of tubulin sheet by taxol: PDB ref IJFF : http://www.pdb.org/pdb/explore/explore.do?structureId=1JFF
Taxol Biosynthesis
Taxol is a complex diterpenoid produced mainly in the bark of the yew tree, genus Taxus.
Taxol is produced in planta as a secondary metabolite. These metabolites are produced in small quantities and are thought to provide an evolutionary benefit for plants in terms of insect or disease protection. In cell suspension cultures, Taxol is produced in very small quantities basally, but when an elicitor is added to the media Taxol production rises dramatically. A common elicitor is methyl jasmonate (MJ), a plant hormone known to activate plant defense pathways in many species. Among other things, MJ activates a cascade resulting in expression of taxol biosynthesis proteins and re-routing of primary metabolism into secondary metabolism.
The first dedicated step of the Taxol biosynthetic pathway is the conversion of geranylgeranyl diphosphate (GGPP), the precursor for all plant diterpenoids, into taxa-4,11-diene. The enzyme catalyzing the conversion of GGPP is taxadiene synthase (TXS), a lyase enzyme. Because TXS relies on Mg2+ metal chemistry to catalyze the reaction it is classified as a class I terpenoid cyclase (citation: Mustafa Köksal, Yinghua Jin, Robert M. Coates, Rodney Croteau & David W. Christianson Nature 469, 116–120 (06 January 2011) doi:10.1038/nature09628)
The remainder of the Taxol biosynthetic pathway comprises approximately 20 steps, of which a few remain unknown. Efforts are currently underway in the Roberts, Walker and Normanly labs to identify the enzyme catalyzing the formation of the oxetane ring moiety in Taxol, which has been shown to be essential for its microtubule binding activity (citation: Expositio taxol paper). The known steps of the Taxol biosynthetic pathway can be seen in Figure X.
Molecular scene 1 - slideshow of metabolites in main structure: taxa-4,11-diene, taxa-4,11-dien-5A-ol, Taxa-4,11-dien 5A 13A diol, 10-deacetyl baccatin III, baccatin III, (side chain), 3,N-debenzoyl Taxol, paclitaxel
Molecular scene 2 - side-chain, Phenylalanine, beta phenylalanine, phenylisoserine
Proteins: taxadiene synthase(3p5r), tcPAM (3nz4)(lyase, catalyzes 1st dedicated step of side chain pathway), phenyalanine aminomutase(2yii) (http://www.pdb.org/pdb/explore/explore.do?structureId=2YII)
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