%0 Journal Article
%T An In-Silico Sequence-Structure-Function Analysis of the N-Terminal Lobe in CT Group Bacterial ADP-Ribosyltransferase Toxins
%J Toxins | An Open Access Journal from MDPI
%D 2019
%R https://doi.org/10.3390/toxins11060365
%X The C3-like toxins are single-domain proteins that represent a minimal mono-ADP-ribosyl transferase (mART) enzyme with a simple model scaffold for the entire cholera toxin (CT)-group. These proteins possess a single (A-domain) that modifies Rho proteins. In contrast, C2-like toxins require a binding/translocation partner (B-component) for intoxication. These are A-only toxins that contain the E-x-E motif, modify G-actin, but are two-domains with a C-domain possessing enzymatic activity. The N-domain of the C2-like toxins is unstructured, and its function is currently unknown. A sequence-structure-function comparison was performed on the N-terminal region of the mART domain of the enzymatic component of the CT toxin group in the CATCH fold (3.90.210.10). Special consideration was given to the N-domain distal segment, the ¦Á-lobe (¦Á 1¨C¦Á 4), and its different roles in these toxin sub-groups. These results show that the role of the N-terminal ¦Á-lobe is to provide a suitable configuration (i) of the ¦Á 2¨C¦Á 3 helices to feature the ¦Á3-motif that has a role in NAD + substrate binding and possibly in the interaction with the protein target; (ii) the ¦Á 3¨C¦Á 4 helices to provide the ¦Á 3/4-loop with protein-protein interaction capability; and (iii) the ¦Á 1-N tail that features specialized motif(s) according to the toxin type (A-only or A-B toxins) exhibiting an effect on the catalytic activity via the ARTT-loop, with a role in the inter-domain stability, and with a function in the binding and/or translocation steps during the internalization process. View Full-Tex
%U https://www.mdpi.com/2072-6651/11/6/365