Beskrivelse
Metabolic channelling mediated by metabolons is thought to improve catalytic efficiencies, avoid metabolic interference, and ensure immediate conversion of labile and/or toxic intermediates. Metabolon formation may be transient and thus difficult to show experimentally. The cyanogenic glucoside dhurrin is produced from tyrosine in a pathway involving two cytochromes P450 (CYP79A1 and CYP71E1), a UDPG-glucosyltransferase (UGT85B1), and the redox partner cytochrome P450 reductase (CPR). Experimental evidence suggests that this pathway is organized as a metabolon. Homology modelling was used to construct three dimensional models of all three membrane proteins involved to gain additional knowledge of catalytic sites, substrate access channels, protein-protein interactions, and the membrane surface interactions of the metabolon. From the proposed protein-protein docking it is clear that metabolon formation is dynamic and the interactions involved are transient. The membrane anchored portion of the metabolon has been reconstituted into nano discs to characterize interactions with the soluble UDPG-glucosyltransferase by surface plasmon resonance spectroscopy in the absence of detergents. We conclude that homology modelling offers new detailed insight in P450 reaction mechanisms and metabolon organization and may be used to design metabolons with new interesting specificities.| Periode | 24 jun. 2009 |
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| Begivenhedstitel | 16th International Conference on Cytochrome P450 |
| Begivenhedstype | Konference |
| Arrangør | Hirofumi Shoun |
| Placering | Okinawa, JapanVis på kort |