Local Function Conservation in Sequence and Structure Space
Figure 8
A) Structural neighbors of hypothetical protein TT1426 (PDB 1wd5) according to TM-align. The image was generated by multidimensional scaling in the same way as Figure 4A. Proteins annotated with GO term GO:0016757 (glycosyltransferase activity) are colored yellow and they form a large group on the lower left, where the query is also located. The glycosyltransferase group is subdivided into subgroups. In general these subgroups are associated with different substrates, in particular adenine phosphoribosyltransferase (d1l1qa, d1g2qa), uracil phosphoribosyltransferase (d1o5oa, d1a3c), or xanthine/hypoxanthine/guanine phosphoribosyltransferases (d1nula, d1hgxa, d1dqna, d1j7ja, d1bzya). Proteins not annotated with GO∶0016757 are colored grey. They are less structurally related to the query than the glycosyltransferases, and accordingly they group separately on the right and top. B) Structural superposition of query TT1426 (PDB 1wd5 [41] in light blue) and the nearest neighbor, xanthine phosphoribosyltransferase (ASTRAL d1nula [45] in gold). The conserved 5-phosphoribosyl-1-pyrophosphate (PRPP)-binding motif characteristic of type I PRTases is colored pink in 1wd5, and violet in d1nula. Residues Arg32 and Lys56 in the query 1wd5 are shown in blue sticks. They are likely to be functionally relevant (involved in binding the pyrophosphate [41]). The structurally equivalent residues in the nearest neighbor are shown in orange. The structural differences in helices α3 and α4, as well as in the substrate binding C-terminal hood region (helices α7 and α8), indicates that they might have different substrates.