Sandbox1111: Difference between revisions
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==Crystal Structure of Human Drug Metabolizing Cytochrome P450 2C8== | ==Crystal Structure of Human Drug Metabolizing Cytochrome P450 2C8== | ||
'''By Amit Shavit''' | '''By Amit Shavit''', 5/21/09 | ||
{{STRUCTURE_3cin | PDB=1pq2 | SCENE= }} | {{STRUCTURE_3cin | PDB=1pq2 | SCENE= }} | ||
==Protein== | |||
CYP2C8 is one of the principal hepatic drug-metabolizing enzymes that oxidizes therapeutic drugs such as taxol and cerivastatin and endobiotics such as retinoic acid and arachidonic acid. This protein has relatively large active site volume [go to Structure section and choose the green link to portray the active sites]. CYP2C8 crystallized as a symmetric dimer and is observed in solution. Furthermore, mass spectrometry confirmed the association of palmitic acid with the enzyme. This novel finding identifies a peripheral binding site in P450s that may contribute to drug-drug interactions in P450 metabolism. Perhaps an implement of Kerpolla's ingenious BiFC could provide a better understanding and monitoring of these drug-drug interactions. | |||
==Structure== | |||
<scene name='Sandbox1111/Polar_bonds/1'>Polar bonds</scene> in dark green | This protein is a dimer. The two subunits of the dimer are visually distinguishable by their different color schemes. Moreover this protein is mostly composed of <scene name='Sandbox1111/Alpha/3'>Alpha Helices</scene>, as shown in blue. While it's initially hard to tell, there are several <scene name='Sandbox1111/Beta/1'>Beta Sheets</scene>, as shown in purple. Furthermore, as most proteins contain a hydrophobic core, this protein indeed contains many <scene name='Sandbox1111/Hydrophobic_red/1'>Hydrophobic interactions</scene>, as shown in red, and relatively fewer <scene name='Sandbox1111/Polar_bonds/1'>Polar bonds</scene>, as shown in dark green. Lastly, the protein's <scene name='Sandbox1111/Active_sites/1'>Active Sites</scene> are shown in brown. | ||
==Reference== | |||
Schoch GA, Yano JK, Wester MR, Griffin KJ, Stout CD, Johnson EF Structure of human microsomal cytochrome P450 2C8. Evidence for a peripheral fatty acid binding site. J Biol Chem. 2004 Mar 5;279(10):9497-503. Epub 2003 Dec 15. PMID:14676196 | |||