From Protein Structure to Function with Bioinformatics.pdf

264 R.A. LaskowskiFig. 10.6 A ligand-binding template match from ProFunc. (a) The three purple residues correspondto a ligand-binding template for a coenzyme A (coa) ligand, shown coloured by atom type(carbon grey, nitrogen blue, oxygen red, sulphur yellow and phosphorus orange). The templateresidues are Asn138, Ser141 and Cys134 from PDB entry 1s7n, a RimL N(α)-acetyltransferasefrom Salmonella typhimurium. The three yellow residues correspond to the residues in the querystructure, PDB entry 2fck, that match the template residues. They are: Asn140, Ser143 andCys136, respectively. The RMSD of the 14 matched side chain atoms is 1.18 Å. (b) As in a, butwith additional matching residues lying within 10 Å of the template’s centre shown. These areresidues of identical residue type which overlap when the query and template structures are superposedon the basis of the template match. The purple residues are from the template structure(1s7n) while the yellow ones are from the query structure (2fck)Reverse TemplatesThe fourth group of templates are intended to find any matches that the first three setsmay have missed. They are the reverse templates which are computed from the targetstructure itself. They are generated using much the same rules as for the ligand- andDNA-binding templates. The main differences are that, firstly, the whole protein structureis considered, rather than merely the residues in contact with ligand or DNA, andsecondly that the weighting of each of the templates is by residue conservation (asobtained from a multiple alignment of the sequences returned by a BLAST searchagainst the UniProt sequence database). The templates are selected so that, ideally,each residue in the protein is present in at least one template, although, if too many aregenerated, their number is capped at twice the number of residues in the sequence.The top reverse template hit to 2fck is shown in Fig. 10.7. The match is to PDBentry 1s7f, a RimL N(α)-acetyltransferase from S. typhimurium. This is the apoform of the 1s7n structure matched by the SSM fold-matching program and theligand-binding templates above.Template Searching and ScoringThe template searches can return hundreds, thousands or even tens of thousandsof matches, particularly in the case of the reverse templates. The problem, then, isto discard fortuitous matches and retain only significant matches, ranked in order