Gogos, A., Jantz, D., Senturker, S., Richardson, D., Dizdaroglu, M., Clarke, N. D.
Assignment of Enzyme Substrate Specificity by Principal Component Analysis of Aligned Protein Sequences: an Experimental Test Using DNA Glycosylase Homologs
Proteins. 2000 Jul 01; 40(1): 98-105.
We have studied the relationship between amino acid sequence and substrate specificity in a DNA glycosylase family by characterizing experimentally the specificity of four new members of the family. We show that principal component analysis (PCA) of the sequence family correctly predicts the substrate specificity of one of the novel homologs even though conventional sequence analysis methods fail to group this homolog with other sequences of the same specificity. PCA also suggested, correctly, that another homolog characterized previously differs in its specificity from those sequences with which it clusters by conventional criteria. These results suggest that principal component analysis of sequence families can be a useful tool in annotating genome sequences when there is ambiguity concerning which subfamily a new homolog belongs to. Published 2000 Wiley-Liss, Inc.