InterPro domain: IPR011765

This entry represents an N-terminal domain found in metallopeptidases and non-peptidase homologues belonging to MEROPS peptidase family M16 (clan ME), subfamilies M16A, M16B and M16C. Members of this family include:

• Insulinase, insulin-degrading enzyme ( 3.4.24.56 )
• Mitochondrial processing peptidase alpha subunit, (Alpha-MPP, 3.4.24.64 )
• Pitrlysin, Protease III precursor ( 3.4.24.55 )
• Nardilysin, ( 3.4.24.61 )
• Ubiquinol-cytochrome C reductase complex core protein I,mitochondrial precursor ( 1.10.2.2 )
• Coenzyme PQQ synthesis protein F ( 3.4.99 )

These proteins do not share many regions of sequence similarity; the most noticeable is in the N-terminal section. This region includes a conserved histidine followed, two residues later by a glutamate and another histidine. In pitrilysin, it has been shown [ 1 ] that this H-x-x-E-H motif is involved in enzymatic activity; the two histidines bind zinc and the glutamate is necessary for catalytic activity.The proteins classified as non-peptidase homologues either have been found experimentally to be without peptidase activity, or lack amino acid residues that are believed to be essential for the catalytic activity.

1. A yeast gene necessary for bud-site selection encodes a protein similar to insulin-degrading enzymes. Nature 372, 567-70