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More Insight On P450 Function

Important enzyme caught with an essential binding partner clarifies how the enzyme metabolizes drugs and other organic molecules

by Sarah Everts
June 10, 2013 | A version of this story appeared in Volume 91, Issue 23

Credit: Science
Putidaredoxin (green) binds to an α-helix in P450 (blue).
P450 in conformation with putidaredoxin
Credit: Science
Putidaredoxin (green) binds to an α-helix in P450 (blue).

Cytochrome P450 enzymes catalyze oxidation reactions essential to the metabolism of organic molecules—including many drugs—in our liver and elsewhere in the body. Researchers solved the X-ray crystal structures of members of this important enzyme family long ago, as well as the structures of a handful of P450 accessory proteins. But the overall topology of the enzyme in a complex with key accessory proteins has remained elusive. Structural biologists Sarvind Tripathi, Huiying Li, and Thomas L. Poulos of the University of California, Irvine, have now determined the structure of a P450 in association with a partner protein called putidaredoxin, which helps the enzyme perform its redox reactions. The accomplishment furthers the structural characterization of the P450-putidaredoxin system (Science 2013, DOI: 10.1126/science.1235797). The team found that putidaredoxin binds to an α-helix unit in P450, the action of which helps establish the proton relay network that is essential for carrying out oxidation. The researchers expect the new insight on the enzyme to help scientists develop improved strategies to activate or metabolize drugs.


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