Conformational Proteomics of Macromolecular Architecture: Approaching the Structure of Large Molecular Assemblies and their Mechanisms of Action

Multifunctional enzyme complexes can reach molecular masses of MDa and above, and exceed the ribosome in size. Covalently attached swinging arms, such as lipoyl groups, biotinyl groups and phosphopantetheinyl groups, are essential to their reaction mechanisms. Unexpectedly, it turns out that protein domains contribute to the processes of molecular recognition that define, channel and protect the substrates and catalytic intermediates. The crucial part played by the mechanical motion of protein domains and the role of the molecular architecture that underlies the interactions of the component enzymes can now be identified and assessed. Such enzymes are better now regarded as sophisticated biological nanormachines.
Keywords: Multienzyme complexes, multifunctional proteins, substrate channeling, self-assembly, nanomachines
The book of life is written in the language of DNA, but the story is made possible only by the activities of myriads of protein molecules. Among the most important of these proteins are the enzymes; without catalysis, a biologically useful time would be years rather than seconds or milliseconds. The normal biological milieu of neutral pH and aqueous solution is inimical ro many chemical reactions. Enzymes make them possible. The basic principles of enzyme...