Abstract: Gas1p is an exocellular glycoprotein of Saccharomyces cerevisiae and plays a crucial role in cell wall assembly, due to its β-(1,3)-glucan transferase activity. The identification of Gas1p homologues in other yeast species and fungi allowed the definition of a new family of glycosyl hydrolases, family GH72, on the basis of sequence similarity. Hydrophobic cluster analysis of the catalytic domain (C-domain) of some GH72 members suggests a (β/α)8 barrel fold, also supported by our recent study on the structural and functional characteristics of the C-domain of Gas1p. Standard homology modelling approaches cannot be used to infer the structure of C-domain of Gas1p and related proteins, due to the lackness of suitable homologues of known 3D structures. Threading and fold recognition approaches have been shown to predict fold of novel proteins with relatively high accuracy. However it should be noted that the detection of possible remote homologues is only the first step of successful modelling. In fact alignment to the same scaffold produced by different threading methods can be significantly dissimilar and affected by local errors, making difficult the derivation of a good structural model. With the aim of unraveling the key molecular characteristics of the C-domain of Gas1p and related proteins, in the present work, a procedure has been worked in which data derived from threading methods, multiple sequence alignments and secondary structure predictions were merged and compared to experimental results in order to obtain reliable and detailed three dimensional models.