1pq2

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{{STRUCTURE_1pq2| PDB=1pq2 | SCENE= }}
{{STRUCTURE_1pq2| PDB=1pq2 | SCENE= }}
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'''Crystal Structure of Human Drug Metabolizing Cytochrome P450 2C8'''
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===Crystal Structure of Human Drug Metabolizing Cytochrome P450 2C8===
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==Overview==
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A 2.7-Angstrom molecular structure of human microsomal cytochrome P450 2C8 (CYP2C8) was determined by x-ray crystallography. The membrane protein was modified for crystallization by replacement of the hydrophobic N-terminal transmembrane domain with a short hydrophilic sequence before residue 28. The structure of the native sequence is complete from residue 28 to the beginning of a C-terminal histidine tag used for purification. 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. Consistent with the relatively large size of its preferred substrates, the active site volume is twice that observed for the structure of CYP2C5. The extended active site cavity is bounded by the beta1 sheet and helix F' that have not previously been implicated in substrate recognition by mammalian P450s. CYP2C8 crystallized as a symmetric dimer formed by the interaction of helices F, F', G', and G. Two molecules of palmitic acid are bound in the dimer interface. The dimer is observed in solution, and 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.
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(as it appears on PubMed at http://www.pubmed.gov), where 14676196 is the PubMed ID number.
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{{ABSTRACT_PUBMED_14676196}}
==About this Structure==
==About this Structure==
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[[Category: Membrane protein]]
[[Category: Membrane protein]]
[[Category: Taxol 6-hydroxylase]]
[[Category: Taxol 6-hydroxylase]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 05:21:20 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jul 28 02:41:13 2008''

Revision as of 23:41, 27 July 2008

Image:1pq2.png

Template:STRUCTURE 1pq2

Crystal Structure of Human Drug Metabolizing Cytochrome P450 2C8

Template:ABSTRACT PUBMED 14676196

About this Structure

1PQ2 is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

Reference

Structure of human microsomal cytochrome P450 2C8. Evidence for a peripheral fatty acid binding site., Schoch GA, Yano JK, Wester MR, Griffin KJ, Stout CD, Johnson EF, J Biol Chem. 2004 Mar 5;279(10):9497-503. Epub 2003 Dec 15. PMID:14676196

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