From Protein Structure to Function with Bioinformatics.pdf

8 3D Motifs 195Table 8.1 (continued)Name and URL Server function 3D motif database aProFuncwww.ebi.ac.uk/thorntonsrv/databases/profuncProKnowProknow.mbi.ucla.eduProtemotprotemot.csbb.ntu.edu.twSuMosumo-pbil.ibcp.fr commercialsite: www.medit.fr/products-page2-medsumo.htmlMulti-search including motifsearch with JESS: wholequery vs. motif database,query fragments vs. wholechains; estimates significanceMulti-search including motifsearches with RIGOR,returns GO annotationsCompares query to all or asubset (enzymes only orspecific class) of ligandbindingmotifsCompares query structure,chain, or ligand-bindingsite to database of structuresor just their ligandbindingsites bActive site motifs from theCSA, 13,057 ligand-bindingand 1,200 DNA-bindingmotifs from individualstructures, 11,750 wholechains; residues are representedby side chain atoms,smaller residues also byone or more backboneatoms10,230 motifs with GOannotations from theirsource structures, 7,819 ifelectronic annotations areexcluded2,362 alpha-carbon bindingsite motifs, 1,051 fromenzymes34,210 ligand-binding sites inaddition to whole structuresdescribed as spatial patternsof functional groupsaFrom publication, web site, or communications with authors; may not be currentbNoncommercial use onlya derived 3D motif could still reflect common ancestry or coincidence rather thanshared function.Interpretation of matches to motifs generated by the “individual structures”method is rather subjective. Often, as in sequence-based inference, annotations aresimply transferred to the query from the source of the best-matching motif. Amatch to a binding site motif might be interpreted conservatively as a prediction ofbinding specificity, but other annotations like catalytic activity, family, and superfamilymight also be inferred (rightly or wrongly). It should be noted that mereproximity to a ligand does not guarantee that a residue is important for binding orcatalysis; substitutions may be well tolerated. Besides using residues near a ligand,another way to derive a motif from a single structure is to use annotations in thePDB file called SITE records. Although these annotations are intended to list residuesin binding sites, the meaning of matches to such motifs is also unclear, sincethere are no definitive criteria as to which residues should be listed. Furthermore,many PDB files of ligand-bound structures do not contain any SITE records.Another important consideration is match stringency, which depends on themotif size and representation and on the qualitative rules and numerical cutoffs