The DOI matches its Crossref record; 58 of the 58 references it cites were found in a registry or an index.
Crystal Structure of Human Cytochrome P450 2D6
Open accessAbstract
Cytochrome P450 2D6 is a heme-containing enzyme that is responsible for the metabolism of at least 20% of known drugs. Substrates of 2D6 typically contain a basic nitrogen and a planar aromatic ring. The crystal structure of human 2D6 has been solved and refined to 3.0A resolution. The structure shows the characteristic P450 fold as seen in other members of the family, with the lengths and orientations of the individual secondary structural elements being very similar to those seen in 2C9. There are, however, several important differences, the most notable involving the F helix, the F-G loop, the B'helix, beta sheet 4, and part of beta sheet 1, all of which are situated on the distal face of the protein. The 2D6 structure has a well defined active site cavity above the heme group, containing many important residues that have been implicated in substrate recognition and binding, including Asp-301, Glu-216, Phe-483, and Phe-120. The crystal structure helps to explain how Asp-301, Glu-216, and Phe-483 can act as substrate binding residues and suggests that the role of Phe-120 is to control the orientation of the aromatic ring found in most substrates with respect to the heme. The structure has been compared with published homology models and has been used to explain much of the reported site-directed mutagenesis data and help understand the metabolism of several compounds.
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Metadata
- Authors
- Rowland, P., Blaney, F. E., Smyth, M. G., Jones, J. J., Leydon, V. R., Oxbrow, A. K., Lewis, C. J., Tennant, M. G., Modi, S., Eggleston, D. S., Chenery, R. J., & Bridges, A. M.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2006-03
- Volume
- 281
- Issue
- 11
- Pages
- 7614-7622
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2105587896
- Cited by
- 437
- References
- 58
- FWCI
- 25.60
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- Rowland, P., Blaney, F. E., Smyth, M. G., Jones, J. J., Leydon, V. R., Oxbrow, A. K., Lewis, C. J., Tennant, M. G., Modi, S., Eggleston, D. S., Chenery, R. J., & Bridges, A. M. (2006). Crystal Structure of Human Cytochrome P450 2D6. Journal of Biological Chemistry. https://doi.org/10.1074/jbc.m511232200
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