|Proteins (2004) 55(2):455-63|
|Northeast Structural Genomics Consortium|
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We have introduced a method to identify functional shifts in protein families. ...
Our method is based on the calculation of an active-site conservation ratio, which we call the "ASC ratio." For a structurally based alignment of a protein family, this ratio is the average sequence similarity of the active-site region compared to the full-length protein. The active-site region is defined as all the residues within a certain radius of the known functionally important groups. Using our method, we have analyzed enzymes of central metabolism from a large number of genomes (35). We found that for most of the enzymes, the active-site region is more highly conserved than the full-length sequence. However, for three tricarboxylic acid (TCA)-cycle enzymes, active-site sequences are considerably more diverged (than full-length ones). In particular, we were able to identify in six pathogens a novel isocitrate dehydrogenase that has very low sequence similarity around the active site. Detailed sequence-structure analysis indicates that while the active-site structure of isocitrate dehydrogenase is most likely similar between pathogens and nonpathogens, the unusual sequence divergence could result from an extra domain added at the N-terminus. This domain has a leucine-rich motif similar one in the Yersinia pestis cytotoxin and may therefore confer additional pathogenic functions.
|metabolism chemistry |
|Binding Sites Humans Amino Acid Motifs Amino Acid Sequence Animals Conserved Sequence Molecular Sequence Data Sequence Alignment Phylogeny Succinate Dehydrogenase Citric Acid Cycle Isocitrate Dehydrogenase Malate Dehydrogenase |
|4 (Last update: 11/10/2018 10:00:44pm)|
|Proteins. 2004 May 1;55(2):455-63.|