Homologous proteins, description

Yamanaka has attempted to use the relative cross-reactivities between cytochromes c of one organism and cytochrome oxidases of another to make a quantitative assessment of evolutionary similarity 440,442,44, and earlier references cited therein). If this method were successful, it would be a powerful adjunct to sequence and structure comparisons since far less material and labor are required to make an activity measurement than to carry out an amino acid sequence analysis or X-ray diffraction study. One critical requirement, of course, is that only strictly homologous proteins are compared. If noncorresponding proteins in two organisms are compared, a spurious estimate of their unrelatedness would be obtained. It is in this context that Yamanaka emphasized the need for a descriptive term for what we have called eukaryotic c. ... 

In reaction with the active heme complex, compound 1, it is often assumed that the first stage is homolytic hydrogen abstraction, resulting in radical formation. This is certainly likely to occur with aliphatic hydroxylation. Ideally a calculation of the transition state should be carried out, but this is difficult in practice. Relative radical stabilities have therefore been used as an approximation. In a typical calculation one generates all possible radicals for a substrate, optimizes them, and determines their relative stabilities. They are then docked into the 3D protein structure using constraints between the heme and the sites predicted from the radical calculations. Early descriptions of this approach made use of homology models, but the same techniques can obviously be used with crystal structures. 

The science community has clearly established the essential role which protein and DNA sequences play in the understanding of biological systems. The sequences themselves are informative Indeed, many software tools are available which allow to make sense of the primary sequence information. Take those that analyse protein sequences for domains and active sites, perform similarity and homology searches, or predict the three-dimensional structure or physico-chemical parameters. However, raw sequences contain insufficient information, per se. One cannot infer any description or understanding of the level of expression of the active proteins, the content of post-translational modifications (PTMs), the tertiary structure and, what is perhaps the most relevant information, a protein s function. Like the sequences themselves, all these added value data need to be captured in various databases. These databases have to be queried by different types of users in proteomics and should therefore be easily searchable by software tools and be inter-linked in order to document the correspondences between the type of information provided by the different databases. 

These proteins show differences in their cycles that have implications for their chaperone activities. We will use the available data to provide for these homologs a comparative description of the mechanistic features of the ATPase cycles, the substrate binding features, the coupling mechanism, and the regulation by co-chaperones. 

---