Most of the 10,000+ structural genomics (SG) protein structures in the PDB are of unknown or uncertain function. We present a novel computational methodology, Structurally Aligned Local Sites of Activity (SALSA), to evaluate functional annotations and predict function. SALSA utilizes the predicted functional residues from THEMATICS and POOL, which in turn are based on computed chemical properties. The members of the crotonase superfamily share very similar overall structures but catalyze a significant range of different biochemical reactions. To date 34 SG proteins have been previously assigned the putative annotation of enoyl-CoA hydratase (crotonase), the parent protein of this superfamily. However, we show that of these 34 SG proteins, only 11 are likely to be correctly annotated, while the 23 others have local spatial patterns that are quite different from enoyl-CoA hydratase. These 23 are likely to be misannotated. In some of these cases, SALSA assigns a more probable biochemical function.

Novel local structure approach to functional characterization of protein structures in the crotonase superfamily

243rd National Meeting (2012)

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