Figure 5

Structural comparison of the P1 pockets in hDNPEP and bacterial M18 members. (A-C) Three bacterial M18 AP structures (PDB ids in brackets) are superimposed onto hDNPEP, with particular focus on the P1 substrate pocket. This highlights variations not only in shape but also residue compositions for the P1 pocket, and may be correlated with different substrate specificities and enzyme activities among M18 enzymes. (D) A structure-based sequence alignment shows no conservation of four key residues of the hDNPEP P1 pocket among the bacterial M18 enzymes, in particular Lys374 likely to be a determinant for acidic amino acid preference.