Protein function annotation with Structurally Aligned Local Sites of Activity (SALSAs)

<p>Abstract</p> <p>Background</p> <p>The prediction of biochemical function from the 3D structure of a protein has proved to be much more difficult than was originally foreseen. A reliable method to test the likelihood of putative annotations and to predict function from structure would add tremendous value to structural genomics data. 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.</p> <p>Results</p> <p>Implementation of the SALSA method is described. For the structural genomics protein PY01515 (PDB ID <ext-link ext-link-id="2aqw" ext-link-type="pdb">2aqw</ext-link>) from <it>Plasmodium yoelii</it>, it is shown that the putative annotation, Orotidine 5'-monophosphate decarboxylase (OMPDC), is most likely correct. SALSA analysis of YP_001304206.1 (PDB ID <ext-link ext-link-id="3h3l" ext-link-type="pdb">3h3l</ext-link>), a putative sugar hydrolase from <it>Parabacteroides distasonis</it>, 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 <it>Nonomuraea flexuosa </it>(PDB ID <ext-link ext-link-id="1m4w" ext-link-type="pdb">1m4w</ext-link>), 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 <it>Mycobacterium avium </it>(PDB ID <ext-link ext-link-id="3q1t" ext-link-type="pdb">3q1t</ext-link>) 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 β-diketone hydrolase from <it>Cyanobacterium anabaena </it>(PDB ID <ext-link ext-link-id="2j5s" ext-link-type="pdb">2j5s</ext-link>). This suggests that the reported ECH function of the SG protein is incorrect and that it is more likely a β-diketone hydrolase.</p> <p>Conclusions</p> <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.</p

Author Correction: Reproducible, interactive, scalable and extensible microbiome data science using QIIME 2

In the version of this article initially published, some reference citations were incorrect. The three references to Jupyter Notebooks should have cited Kluyver et al. instead of Gonzalez et al. The reference to Qiita should have cited Gonzalez et al. instead of Schloss et al. The reference to mothur should have cited Schloss et al. instead of McMurdie & Holmes. The reference to phyloseq should have cited McMurdie & Holmes instead of Huber et al. The reference to Bioconductor should have cited Huber et al. instead of Franzosa et al. And the reference to the biobakery suite should have cited Franzosa et al. instead of Kluyver et al. The errors have been corrected in the HTML and PDF versions of the article.</p

QIIME 2: Reproducible, interactive, scalable, and extensible microbiome data science

Bolyen E, Rideout JR, Dillon MR, et al. QIIME 2: Reproducible, interactive, scalable, and extensible microbiome data science. PeerJ. 2018

Reproducible, interactive, scalable and extensible microbiome data science using QIIME 2

An amendment to this paper has been published and can be accessed via a link at the top of the paper