| Structural highlights
4jlt is a 1 chain structure with sequence from European rabbit. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Ligands: | , , , , , |
| Related: | 2q6n, 3kw4, 2bdm, 1suo, 3me6, 3mvr, 3g5n, 3r1a, 3r1b, 3g93, 1po5, 3uas, 4h1n, 3tk3, 3tmz |
| Gene: | CYP2B4 (European rabbit) |
| Activity: | Unspecific monooxygenase, with EC number 1.14.14.1 |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
[CP2B4_RABIT] Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. In the epoxidation of arachidonic acid it has a unique preference for the 5,6-olefin.
Publication Abstract from PubMed
An X-ray crystal structure of CYP2B4 in complex with the drug paroxetine [(3S,4R)-3-[(2H-1,3-benzodioxol-5-yloxy)methyl]-4-(4-fluorophenyl)piperidine] was solved at 2.14 A resolution. The structure revealed a conformation intermediate to that of the recently solved complex with amlodipine and that of the more compact complex with 4-(4-chlorophenyl)imidazole in terms of the placement of the F-G cassette. Moreover, comparison of the new structure with 15 previously solved structures of CYP2B4 revealed some new insights into the determinants of active-site size and shape. The 2B4-paroxetine structure is nearly superimposable on a previously solved closed structure in a ligand-free state. Despite the overall conformational similarity among multiple closed structures, the active-site cavity volume of the paroxetine complex is enlarged. Further analysis of the accessible space and binding pocket near the heme reveals a new subchamber that resulted from the movement of secondary structural elements and rearrangements of active-site side chains. Overall, the results from the comparison of all 16 structures of CYP2B4 demonstrate a cluster of protein conformations that were observed in the presence or absence of various ligands.
A Structural Snapshot of CYP2B4 in Complex with Paroxetine Provides Insights into Ligand Binding and Clusters of Conformational States.,Shah MB, Kufareva I, Pascual J, Zhang Q, Stout CD, Halpert JR J Pharmacol Exp Ther. 2013 Jul;346(1):113-20. doi: 10.1124/jpet.113.204776. Epub , 2013 Apr 30. PMID:23633618[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Shah MB, Kufareva I, Pascual J, Zhang Q, Stout CD, Halpert JR. A Structural Snapshot of CYP2B4 in Complex with Paroxetine Provides Insights into Ligand Binding and Clusters of Conformational States. J Pharmacol Exp Ther. 2013 Jul;346(1):113-20. doi: 10.1124/jpet.113.204776. Epub , 2013 Apr 30. PMID:23633618 doi:10.1124/jpet.113.204776
|
