Since significant variations in the amino acid sequence within a protein family still yield very similar three-dimensional structures, we say that structure has a higher degree of conservation than sequence. This can be understood if we consider function – for example, binding a ligand, specificity of interactions with other proteins, and structural dynamics – all depend on the three-dimensional structure. Therefore, determining the structure of a protein of unknown function and its subsequent comparison to other known structures in a database may help reveal structural homologs and, ultimately, the protein's function. The principle of structure conservation also allows us to rely on structure prediction and modeling when no experimental structure is available.
An exciting example of structure conservation was provided by the anaerobic cobalt chelatase, an enzyme active in vitamin B12 synthesis (Schubert et al., 1999
). Although the protein's function was already known, only the determination of its three-dimensional structure revealed its similarity to the structure of ferrochelatase (Al-Karadaghi et al., 1997
), an enzyme active in heme biosynthesis. The reason is that the sequence identity between the two proteins is only 11%, a number much smaller than the so-called "homology threshold" (around 20-25% sequence identity). The similarity between the two structures strongly suggested a common evolutionary origin of the two proteins and a similarity in the mechanism of the enzymatic reaction.