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== | ==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== | ==Structure== | ||
<scene name='Sandbox1111/ | 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. | ||
<scene name='Sandbox1111/ | |||
<scene name='Sandbox1111/Hydrophobic_red/1'>Hydrophobic interactions</scene> in red | |||
<scene name='Sandbox1111/Polar_bonds/1'>Polar bonds</scene> in dark green | |||
<scene name='Sandbox1111/Active_sites/1'>Active Sites</scene> are shown in brown | |||
==Reference== | ==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 | 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 | ||
Latest revision as of 07:04, 22 May 2009
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Crystal Structure of Human Drug Metabolizing Cytochrome P450 2C8Crystal Structure of Human Drug Metabolizing Cytochrome P450 2C8
By Amit Shavit, 5/21/09
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| 3cin, resolution 1.70Å () | |||||||||
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| Ligands: | , , | ||||||||
| Gene: | TM1419, TM_1419 (Thermotoga maritima MSB8) | ||||||||
| Activity: | Inositol-3-phosphate synthase, with EC number 5.5.1.4 | ||||||||
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| Resources: | FirstGlance, OCA, RCSB, PDBsum, TOPSAN | ||||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||||
ProteinProtein
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.
StructureStructure
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 , as shown in blue. While it's initially hard to tell, there are several , as shown in purple. Furthermore, as most proteins contain a hydrophobic core, this protein indeed contains many , as shown in red, and relatively fewer , as shown in dark green. Lastly, the protein's are shown in brown.
ReferenceReference
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