Divergent enolase

Figure 10.11 Comparison of the structures of MR, MLE and enolase showing the two homologous domains that illustrate divergent evolution. (From Gerlt et al., 2005. Copyright 2005, with permission from Elsevier.)...

Gerlt, J.A., Babbitt, P.C. and Rayment, I. (2005) Divergent evolution in the enolase superfamily the interplay of mechanism and specificity, Arch. Biochem. Biophys., 433, 59-70. 

In addition to the sequence similarities, structural similarities are evident among the six divergent members of the superfamily that have been structurally characterized. These include MR, MLE, and GlucD, as previously cited, as well as enolase (Lebioda and Stec, 1988 Lebioda and Stec, 1991 Wedekind et al., 1995 Larsen et al., 1996). These, along with preliminary structural characterization of two other superfamily members, GalD (J. Clifton, S. Wieczorek, J. Gerlt, and G. Petsko, unpub-... 

One must be aware, however, of the explicit assumptions that are made in using these methods. For example, with the ET method, multiple homologous sequences are required and it is assumed that ( ) a protein family retains its fold across family members (2) the location of functional sites within a family are conserved (3) functional sites have distinctly lower mutation rates relative to the entire structure and (4) variations in functional sites within groups in a family are due to mutation events that cause divergence. Additionally, manual adjustment of the sequence alignments has also been performed. While these assumptions have been shown to be valid for the cases that Lichtarge has published, this method has not been used across very distantly related proteins such as those proteins in the enolase superfamily. 

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