PMC:2667511 / 41832-45913 JSONTXT

{"target":"https://pubannotation.org/docs/sourcedb/PMC/sourceid/2667511","sourcedb":"PMC","sourceid":"2667511","source_url":"https://www.ncbi.nlm.nih.gov/pmc/2667511","text":"Inference of Subtypes\nSome rules which share the same sets of properties but differ in their value ranges or have other properties can be effective in order to compare features of different interaction types or to identify subtypes in a PPI type. For example, among the top 30% rules, Rules 38 (Table 7) and 16 (Table 6) describe types ENZ and nonENZ respectively, using the same set of properties such as number of atoms and df-ASA. However, their values imply that the interaction sites of nonENZ (Rule 16) are larger than those of ENZ (Rule 38). The ranges of size scales of interaction sites in ENZ are presented in Rules 35, 38 and 46 (Table 7) that share the same set of properties but differ in their values. The overall size of interaction sites in ENZ are described by Rule 38 with the highest confidence among those rules encoding the size of interaction sites. These are interesting cases where the structural difference between types can be directly inferred and subtypes of a PPI type can be derived by grouping different features of interaction sites. We deduced five subtypes of ENZ and a hierarchical tree (Figure 4) to account for those subtypes. We compiled a list of representative association rules (Table 7) to show structural features different among these subtypes.\nFigure 4 A hierarchical tree for supporting inference of subtypes. A hierarchical tree drawn from association rules (Table 7) represents different structural groups in ENZ. Enzyme-inhibitor interactions are characterized with size scales of interaction sites (number of atoms and df-ASA) and SSE content information (helix content). These differences of structural groups result in subtypes of PPIs. Letters in red are identifiers of rules (Tables 6 and 7) to split branches of a tree. Dashed lines show interaction between enzymes and inhibitors in different subtypes. We note that interaction sites of enzymes are distinguished from those of inhibitors in enzyme-inhibitor complexes. Interaction sites for inhibitors are relatively small, i.e., mainly \u003c 1000 Å^2 (Rules 34, 35, 37, 38 and 46), and are made up of strands (Rule 41) and mostly non-regular regions (Rules 1, 4 and 6) without helix content (Rule 3, 28, 29, 30, 32, and 33) which is very informative in order to characterize inhibitors. Remarkably Rules 30 and 28 generalize common features of inhibitors with respect to the size of interaction sites and SSE content. As Rule 29 was considered to be very discriminative to differentiate ENZ from other types, it can depict characteristics of a small group of inhibitors with indicating that inhibitors in SCOP class 7 do not contain helix in interaction sites (Figure 3(a), (b) and 3(c)).\nIn contrast, enzymes have larger interaction sites than their inhibitors and form mixtures of helices and strands in interaction sites (Rules 40, 48, 49, 50 and 51). Both Rules 33 and 40 show that enzymes (Rule 40) have SSEs twice as many as inhibitors (Rule 33). This indicates that both enzymes and inhibitors may contain mainly strands as regular SSEs in interaction sites since enzymes are included in SCOP class 2 (mainly β) and inhibitors do not contain helices in interaction sites. This suggests that non regular regions and beta strands are mainly involved in the interfaces of enzyme-inhibitor interactions. Such extracted information can be useful for the prediction of interaction sites for enzyme-inhibitor complexes. This observation is demonstrated by some small inhibitors in Type ENZ_A (1tabi_, 2ptci_, and 4sgbi_) and Type ENZ_B (1mcti_). Those inhibitors interact with enzymes in Type ENZ_B. The enzymes described by Rules 40, 41 and 43 are included in SCOP superfamily trypsin-like serine proteases (2.47.1) and the inhibitors are mainly in SCOP class 7 which is composed of small proteins dominated by metal ligand, heme, and disulfide bridges.\nIt is possible in a similar way to infer subtypes of other PPI types. Among PPI types, ENZ has plenty of rules (a total of 65) to derive subtypes. Hence, the comparative analysis of association rules was presented for ENZ.","divisions":[{"label":"title","span":{"begin":0,"end":21}},{"label":"p","span":{"begin":22,"end":1288}},{"label":"figure","span":{"begin":1289,"end":1859}},{"label":"label","span":{"begin":1289,"end":1297}},{"label":"caption","span":{"begin":1299,"end":1859}},{"label":"p","span":{"begin":1299,"end":1859}},{"label":"p","span":{"begin":1860,"end":2692}},{"label":"p","span":{"begin":2693,"end":3858}}],"tracks":[]}