Crystallization of Cytochromes P450 and Substrate-Enzyme Interactions

Author(s): Huiying Li , Thomas L. Poulos .

Journal Name: Current Topics in Medicinal Chemistry

Volume 4 , Issue 16 , 2004

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Our understanding of structure-function relationships have made considerable advances owing to the increasing number of new P450 crystal structures. This is especially true with mammalian P450s. As always, the main bottleneck in a structure determination project is crystallization. While the crystallization techniques used for P450 crystal growth are not much different from that utilized for other proteins, special protein engineering strategies have been developed in order to generate soluble, homogeneous membrane-bound P450 samples amendable for crystallization. Newly determined P450 structures also provide convincing evidence that P450 enzymes are highly dynamic and flexible. Common structural elements found in all P450s have been identified that undergo large conformational changes to allow substrate access and product release. In addition, flexible regions may enable the active site to adapt to the binding of substrates of different size, shape, and polarity. This review will focus on the successful membrane P450 crystallization techniques and the new structural insights based on the growing P450 structure database.

Keywords: cytochrome p450, crystallization, crystal structure, substrate-enzyme interaction

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Article Details

Year: 2004
Page: [1789 - 1802]
Pages: 14
DOI: 10.2174/1568026043387205
Price: $58

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