| Date |
January 23, 2006 |
| Speaker |
Prof. Kosuke Morikawa, Institute for Protein Research, Osaka University |
| Title |
Substrate Channeling Mechanism as Revealed from the Crystal Structure of a Fatty Acid Beta-oxidation Multienzyme Complex |
| Abstract |
The atomic view of the active site coupling termed channelling is a major subject in molecular biology. Fatty acid metabolism, linked to energy storage and human obesity, frequently involves multifunctional enzyme complexes, which catalyze sequential reactions through this efficient mechanism. We have determined two distinct crystal structures of the bacterial multienzyme complex that catalyzes the last three sequential reactions in the fatty acid beta-oxidation cycle. The alpha2beta2 heterotetrameric protein shows the uneven ring architecture, which undergoes striking alterations in the positional relationships among the three reaction centers, coupled with the binding of substrate analogues. This domain rearrangement is closely connected to the deformation of an alpha-helical linker, which is conserved in multienzymes and interacts with substrate analogues. The versatile architecture of the complex, with its functionally profound domain and subunit movements, suggests how the individual catalytic components orchestrate the channelling mechanism of fatty acid beta-oxidation. This channelling mechanism could be applied to other beta-oxidation multienzymes, as revealed from the homology model of the human mitochondrial trifunctional enzyme (TFE) complex homologous to bacterial enzymes. |
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