Structure-function analysis of Sedolisins: evolution of tripeptidyl peptidase and endopeptidase subfamilies in fungi.

摘要: Sedolisins are acid proteases that related to the basic subtilisins. They have been identified in all three superkingdoms but not ubiquitous, although fungi secrete acids as part of their lifestyle can up six paralogs. Both TriPeptidyl Peptidase (TPP) and endopeptidase activity it has suggested these correspond separate subfamilies. We studied eukaryotic sedolisins by computational analysis. A maximum likelihood tree shows one major clade containing non-fungal sequences only two well minor clades fungal sequences. One contains known TPPs whereas other characterized endosedolisins. four Cluster Specific Inserts (CSIs) endosedolisins, which CSIs 1, 3 4 appear solvent exposed according structure modeling. Part CSI2 is a short stretch forms novel partially buried α-helix induces conformational change near binding pocket. also total 15 specificity determining positions (SDPs) five, independent analyses, form highly connected SDP sub-networks. Modeling virtual mutants suggests key role for W307A or F307A substitution. The remaining SDPs physically interact at interface catalytic domain enzyme’s prosegment. indeed required compensate induced A307. small concerns subfamily 213 sequences, mostly similar TPP differs, interestingly, position 307, showing isoleucine threonine. Analysis confirms there least sedolisin subfamilies fungi: endopeptidases, third with unknown characteristics. Sequence functional diversification was centered around SDP307 resulted Mutual Information network analysis useful instrument corroboration predicted SDPs.