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We report on a new method, Structurally Aligned Local Sites of Activity (SALSA), for the prediction of biochemical function based on a local structural match at the predicted catalytic or binding site.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>Implementation of the SALSA method is described. For the structural genomics protein PY01515 (PDB ID 2aqw) from <jats:italic>Plasmodium yoelii<\/jats:italic>, it is shown that the putative annotation, Orotidine 5'-monophosphate decarboxylase (OMPDC), is most likely correct. SALSA analysis of YP_001304206.1 (PDB ID 3h3l), a putative sugar hydrolase from <jats:italic>Parabacteroides distasonis<\/jats:italic>, shows that its active site does not bear close resemblance to any previously characterized member of its superfamily, the Concanavalin A-like lectins\/glucanases. It is noted that three residues in the active site of the thermophilic beta-1,4-xylanase from <jats:italic>Nonomuraea flexuosa<\/jats:italic> (PDB ID 1m4w), Y78, E87, and E176, overlap with POOL-predicted residues of similar type, Y168, D153, and E232, in YP_001304206.1. The substrate recognition regions of the two proteins are rather different, suggesting that YP_001304206.1 is a new functional type within the superfamily. A structural genomics protein from <jats:italic>Mycobacterium avium<\/jats:italic> (PDB ID 3q1t) has been reported to be an enoyl-CoA hydratase (ECH), but SALSA analysis shows a poor match between the predicted residues for the SG protein and those of known ECHs. A better local structural match is obtained with Anabaena beta-diketone hydrolase (ABDH), a known \u03b2-diketone hydrolase from <jats:italic>Cyanobacterium anabaena<\/jats:italic> (PDB ID 2j5s). This suggests that the reported ECH function of the SG protein is incorrect and that it is more likely a \u03b2-diketone hydrolase.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>A local site match provides a more compelling function prediction than that obtainable from a simple 3D structure match. The present method can confirm putative annotations, identify misannotation, and in some cases suggest a more probable annotation.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1186\/1471-2105-14-s3-s13","type":"journal-article","created":{"date-parts":[[2013,3,1]],"date-time":"2013-03-01T01:44:31Z","timestamp":1362102271000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Protein function annotation with Structurally Aligned Local Sites of Activity (SALSAs)"],"prefix":"10.1186","volume":"14","author":[{"given":"Zhouxi","family":"Wang","sequence":"first","affiliation":[]},{"given":"Pengcheng","family":"Yin","sequence":"additional","affiliation":[]},{"given":"Joslynn S","family":"Lee","sequence":"additional","affiliation":[]},{"given":"Ramya","family":"Parasuram","sequence":"additional","affiliation":[]},{"given":"Srinivas","family":"Somarowthu","sequence":"additional","affiliation":[]},{"given":"Mary Jo","family":"Ondrechen","sequence":"additional","affiliation":[]}],"member":"297","published-online":{"date-parts":[[2013,2,28]]},"reference":[{"key":"5702_CR1","doi-asserted-by":"publisher","first-page":"489","DOI":"10.1093\/nar\/gkg068","volume":"31","author":"J Westbrook","year":"2003","unstructured":"Westbrook J, Feng Z, Chen L, Yang H, Berman HM: The Protein Data Bank and structural genomics. 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