From Protein Structure to Function with Bioinformatics.pdf

276 J.D. Watson and J.M. ThorntonTable 11.1 Summary of functional predictions and their origins for large-scale analyses. The table shows a summary of the examples discussed in reviewswhich attempt to address the effectiveness of structure-based function prediction using structural genomics targets. For each of the proteins in the articlesdescribed in Section 11.3, a simple summary of the analysis performed is given along with crosses in the appropriate columns indicating which of the structure-basedapproaches was most informativeStudy Protein DescriptionKim et al. (2003) MJ0882 Putative methyltransferase through fold similarity– later experimentally verified.Watson et al.(2007)Adams et al.(2007)MJ0577 Bound ATP suggested an ATP hydrolysis function.TM841 Bound palmitate molecule demonstrated fattyacid binding.MJ0226 Novel fold but weak similarity to nucleotidebinding proteins and HAM1 protein.MJ0285 Multimeric assembly forms a hollow spherewith “windows”. Prompted question as tothe nature of action.MPN625 Two conserved cysteine residues found to lie inthe cleft of a putative active site. This siteresembles those in the 2-cysteine peroxiredoxinfamily.BioH Novel carboxylesterase. Enzyme active-sitetemplate search identifies the catalytic triadIsdG Fold comparison and reverse templates methodsindicate a monooxygenase function.ChuS Three of the four conserved histidine residuesfound adjacent to or pointing into one oftwo large clefts. Shows unusual haem coordination.Fold or assembly(see Chapter 6)XXXKey analyses providing functional cluesSurface/cleft (seeChapter 7)X XXXTemplate (seeChapter 8) Bound ligandXXX