Signal peptide peptidase A (SppA), a serine protease, has catalytic Ser-Lys dyad
Signal peptide peptidase A (SppA; Peptidase S49; Protease IV): SppA is found in all three domains of life and is involved in the cleavage of signal peptides after their removal from the precursor proteins by signal peptidases. This subfamily contains members with either a single domain (sometimes referred to as 36K type), such as sohB peptidase, protein C and archaeal signal peptide peptidase, or an amino-terminal domain in addition to the carboxyl-terminal protease domain that is conserved in all the S49 family members (sometimes referred to as 67K type), similar to E. coli and Arabidopsis thaliana SppA peptidases. Site-directed mutagenesis and sequence analysis have shown these SppAs to be serine proteases. The predicted active site serine for members in this family occurs in a transmembrane domain. Mutagenesis studies also suggest that the catalytic center comprises a Ser-Lys dyad and not the usual Ser-His-Asp catalytic triad found in the majority of serine proteases. Interestingly, the single membrane spanning E. coli SppA carries out catalysis using a Ser-Lys dyad with the serine located in the conserved carboxy-terminal protease domain and the lysine in the non-conserved amino-terminal domain.
Comment:The N- and C-terminal halves of SppA in E. coli are tandem repeats and the Ser/Lys dyad is arranged such that the nucleophile Ser is located in the C-terminal half whereas the general base Lys is located in the N-terminal half.
Structure:3BEZ: Escherichia coli Signal peptide peptidase A (SppA) - View structure with Cn3D
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