InterPro domain: IPR011249

This entry represents domains with a two-layer alpha/beta structure found in metalloenzymes such as LuxS (S-ribosylhomocysteinase; 4.4.1.21 ) and metallopeptidases belonging to MEROPS peptidase family M16. These domains share the same active site motif of HxxEH located in the first core helix, but differ in one of the metal-binding residues. LuxS, the AI-2 (autoinducer-2) producing enzyme for quorum sensing in bacteria, is a homodimeric iron-dependent metalloenzyme containing two identical tetrahedral metal-binding sites similar to those found in peptidases and amidases, although it contains an extra N-terminal strand [ 1 , 2 ]. Some M16 family metallopeptidases, such as mitochondrial processing peptidase (MPP), share the same common fold elaborated with many extra additional structures [ 3 ]. These peptidases usually contain a duplication of this domain, although only the N-terminal domain binds the catalytic metal.

Domains found in metallopeptidases and non-peptidase homologues belonging to MEROPS peptidase family M16 (clan ME), subfamilies M16A, M16B and M16C; 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 )

1. Crystal structure of S-ribosylhomocysteinase (LuxS) in complex with a catalytic 2-ketone intermediate. Biochemistry 44, 3745-53
2. Crystal structure of the quorum-sensing protein LuxS reveals a catalytic metal site. Proc. Natl. Acad. Sci. U.S.A. 98, 11169-74
3. Crystal structures of mitochondrial processing peptidase reveal the mode for specific cleavage of import signal sequences. Structure 9, 615-25