Rossmann-type fold

As already discussed in Chapter 11, there are more than 10 000 protein structures known but only about 30 3D structure types. This might be traced to a limited number of possible stable polypeptide structures but most probably reflects the evolutionary history of the diversity of proteins. There are structural motifs which repeat themselves in a multitude of enzymes which are otherwise neither structurally nor functionally related, such as TIM barrel proteins, four-helix bundle proteins, Rossmann folds, or a/j3-folds of hydrolases (Figure 16.1). 

The first member of the GT-A superfamily fold was identified in 1999 when the three-dimensional stmcture of SpsA was reported (19). This enzyme from Bacillus subtilis is involved in the formation of the spore coat and is a member of the Leloir type of GTs given its apparent use of nucleotidyl-diphospho-donor sugars as a substrate. Enzymes with the GT-A fold have an N-terminal a/p/a sandwich motif that resembles a Rossmann motif and is involved in nucleotide donor binding. Most GT-A fold enzymes also have a characteristic Asp-Xxx-Asp (DXD) or equivalent motif (EXD or TDD) near the center of the protein that coordinates to the phosphate in nucleotide donors via a divalent metal cation (Mn + or Mg +). These motifs are present in the structure of the bovine pi,4-galactosyltransferase I (5) (Fig. 4a). 

The second class of proteins in the aZ/S family of folds contains a large open sheet formed from mostly parallel /3-strands with helices on both sides. In contrast to the TIM barrel there are fewer limitations on the number of strands within the sheet and may vary from 4 to 10. The first example of this type of fold was seen in lactate dehydrogenase which contains a motif that is widely observed in dinucleotide binding proteins (this motif is often referred to as the Rossmann fold) and was the first example of a domain superfamily (Fig. 14b). The observation of a common fold in the dehydrogenases by Rossmann and coworkers started the entire field of structural comparison and study of structural evolution. 

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