Ncluded in the first rigid region. FlexProt creates an alignment of 513 residues with a flexible RMSD of 2.87 ? Three hinge-points dividing the structure in four fragments are identified. As in the FATCAT alignment, the apical domain is kept separate from the rest PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/25609842 of the structure. Even if the C-terminal parts of the hinge and equatorial domains are separated by a hinge point, their N-terminal counterparts are kept together including the stem loop. In general, the alignments produced by FATCAT and FlexProt tend to underestimate the number of hinges for this pair of structures and cannot be used to highlight the difference between the equatorial and hinge domains, nor the different conformation of the stem loop. A correct delineation of the domains is of particular interest in this case. In fact, the identified domains can be used as rigid bodies for the interpretation of low-resolution electron density maps for GroEL in different functional states as determined by electron microscopy. In this way, they allow to derive conclusions at the atomic level from lower resolution data (e. g. Ranson et al. [40]).Human kinase structures Protein kinases are multi-domain proteins catalyzing the phosphorylation of proteins and play important roles in controlling many cellular processes (chapter 13 in [41]). The protein kinase catalytic domain consists of two lobes, a small N-terminal lobe and a large C-terminal lobe connected by a hinge region and is often augmented by other domains that serve in regulation of the kinase activity. Prominent examples of such domains are the SH2 and SH3 domains present in protein kinases such as src Hck kinase [42] and Bcr-abl kinase [43]. In protein kinases, the relative positions and orientations of the different domains are very variable and depend on many factors such as the binding of ligands in the active site and/or the presence of regulating factors.We used RAPIDO to perform an all-against-all alignment for 68 structures of human protein kinases (2278 alignments in total). For comparison, for every pair of structures, an alignment was also determined using DaliLite Ver. 2.4.4 (the standalone version of DALI). Alignments produced by RAPIDO and DALI are compared in Figure 4 and summarized in additional file 1. In terms of overall length, the majority of the alignments are comparable. However, for some cases, the RAPIDO alignments are substantially longer than the DALI alignments (blue and red dots in Figure 4). Three of these cases (blue dots in Figure 4a) correspond to alignments between the structures of Hck from Human (1AD5, [42]), c-Src from Human (1FMK, [44]), Csk from Rat (1K9A, [45]) and c-Abl from Mouse (1OPK, [43]). In these four structures, the kinase domain was crystallized in the presence of SH2 and SH3 domains. Depending on the functional state of the kinase, the SH2 and SH3 domains can be in substantially different positions with respect to the kinase domain. Such different positions can cause rigid aligners not to recognize all domains as similar. For the case of the alignments between Hck and Csk, and between c-Src and Csk (dots in the red circle in Figure 4a), DALI aligns only 329 and 350 residues respectively with the Litronesib cost aligned residues being located in the protein kinase domain and in the SH2 domain. The SH3 domain is not included in the alignment. For the alignment between Csk and c-Abl (dot in the green circle in Figure 4a) DALI aligns only the protein kinase domain. The alignment produced by R.
