Structure neighbours are a rich source of biological annotation. Figure shows an example, the structure neighbours of the SH2 domain of 1QCF. The structure of loop regions contributing to the intra-molecular phosphotyrosine binding site is preserved in 1JYR, a complex of Grb2 SH2 domain with a phosphotyrosine-containing peptide (9
), and in 1FBV, a complex of c-Cbl with a phosphotyrosine-containing peptide (10
). One may infer that proteins preserving this site are likely to bind phosphotyrosine. Consistent with this inference, structure 1G99, an Archaeal acetate kinase (11
), does not preserve this site. If this protein shares a common ancestor with SH2 domains, it presumably belongs to a lineage that diverged prior to evolution of phophotyrosine binding. While superpositions based on 3D domains are normally adequate for structure-function analyses of this kind, Cn3D's alignment editing tools may be used to modify alignments and superpositions when necessary.
Figure 2 MMDB's ‘VAST summary’ of selected structure neighbours of the SH2 domain (3D domain 2) of Hck kinase/1QCF. The locations of loop regions whose conformation is conserved in Grb2/1JYR and c-Cbl/1FBV are highlighted (more ...)
On average, there are over 600 structure neighbours for each 3D domain in MMDB. To help identify neighbours that provide useful annotation, Entrez's ‘VAST Summary’ provides a series of controls for selecting and sorting structure neighbours. As illustrated in Figure , the ‘alignment footprint’ of each neighbour indicates the region on the 3D domain serving as query that can be well superposed onto that neighbour. This display identifies structure neighbours similar to one another, where visualization of multiple-structure superpositions is informative. Other controls sort structure neighbours by measures of similarity and select subsets that include only one representative of sequence-similar subgroups. VAST-Search, which identifies neighbours of user-submitted structures, provides the same analysis tools.