Known allosteric proteins have central roles in genetic disease
Fig 2
Allosteric proteins are overrepresented in disease, and are central in disease-protein networks.
A) Allosteric proteins are significantly more frequently involved in disease than non-allosteric proteins, irrespectively of their quaternary structure. * In the ‘All’ category the number of non-allosteric proteins was defined as human SwissProt proteins minus all human allosteric proteins. Note that the ‘All’ category includes also the proteins where quaternary structure is not known. B) Allosteric proteins (except homomers) are involved in significantly more diseases than non-allosteric ones. C) Allosteric proteins, particularly the ones forming heteromeric complexes have significantly higher betweenness centrality in the disease-network than non-allosteric ones. D-E) Drug-targets have generally higher betweenness centralities than non-drug target proteins, however, allosteric proteins have significantly higher betweenness than non-allosteric proteins in both groups. F) The disease-protein network. Allosteric proteins are represented by red nodes, non-allosteric ones by blue, the size of the nodes was calculated as 1 + Log(nr of diseases). The largest connected component was visualized with the OpenOrd algorithm of the Gephi platform.