Sweet-tasting protein monellin is related to the cystatin family of thiol proteinase inhibitors.

The structure of the intensely sweet protein monellin, isolated from an African berry, and the structures of two thiol proteinase inhibitors, cystatin and stefin B, are found to be very similar. An alignment of sequences of monellin and the inhibitors, deduced from the structural comparisons, has been extended to include other members of the cystatin superfamily. There is a significant homology (up to 23% identical residues) with oryzacystatins, the only well defined plant cystatins. These results clearly indicate that monellin is a close relative of cystatins. Monellin and cystatins do not have the same sequence in the regions homologous to the cystatin active site. It is suggested here, however, that this region in monellin may be essential for a function in situ, because one of the loops comprising this part of the structure is found to be cleaved.