Zinc-endoprotease fold

Figure 8. Superposition of the N-terminal domain of thermolysin (silver) and the catalytic domain of collagenase (orange). Stereo ribbon diagram illustrating the common topology between representative structures of the long spacer (silver) and short spacer (orange) families defining the zinc-endoprotease fold.

Figure 14. Zinc endoproteases a structural superfamily. The central panel shows the superposition of the alpha carbon atoms of the topologically equivalent catalytic domains of proteins from the long consensus family (silver) and the short spacer family (orange). Various consensus sequences are given (see text) with the zinc-chelating residues shown in white. Full blue arrows indicate presence of motif in observed three-dimensional structures corresponding to the zinc endoprotease fold shown in the central panel. Dotted lines indicate putative structure-sequence relationships discussed in the text.

The growing family of known divalent cation-dependent proteases such as insulinase [51] and dibasic convertase [52], with the variant consensus HxxeH, also present interesting questions as to the possibility of a mirrored active site with or without conservation of the overall topology. Conversely, it is possible that entirely different proteins which have no zinc dependency and completely separate function may adopt the zinc endoprotease topology, simply because this fold provides a stable modular scaffold useful in the construction of multidomain proteins. Results of further structural studies are eagerly awaited. 

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