6FPC
Structure of the PRO-PRO endopeptidase (PPEP-2) from Paenibacillus alvei
Summary for 6FPC
| Entry DOI | 10.2210/pdb6fpc/pdb |
| Descriptor | PRO-PRO endopeptidase, ZINC ION, CADMIUM ION, ... (5 entities in total) |
| Functional Keywords | endopeptidase, metalloprotease, zinc, hydrolase |
| Biological source | Paenibacillus alvei More |
| Total number of polymer chains | 4 |
| Total formula weight | 87775.53 |
| Authors | Weeks, S.D.,Klychnikov, O.I.,Hensbergen, P.J.,Strelkov, S.V. (deposition date: 2018-02-09, release date: 2018-05-30, Last modification date: 2024-05-08) |
| Primary citation | Klychnikov, O.I.,Shamorkina, T.M.,Weeks, S.D.,van Leeuwen, H.C.,Corver, J.,Drijfhout, J.W.,van Veelen, P.A.,Sluchanko, N.N.,Strelkov, S.V.,Hensbergen, P.J. Discovery of a new Pro-Pro endopeptidase, PPEP-2, provides mechanistic insights into the differences in substrate specificity within the PPEP family. J. Biol. Chem., 293:11154-11165, 2018 Cited by PubMed Abstract: Pro-Pro endopeptidases (PPEPs) belong to a recently discovered family of proteases capable of hydrolyzing a Pro-Pro bond. The first member from the bacterial pathogen (PPEP-1) cleaves two cell-surface proteins involved in adhesion, one of which is encoded by the gene adjacent to the gene. However, related PPEPs may exist in other bacteria and may shed light on substrate specificity in this enzyme family. Here, we report on the homolog of PPEP-1 in , which we denoted PPEP-2. We found that PPEP-2 is a secreted metalloprotease, which likewise cleaved a cell-surface protein encoded by an adjacent gene. However, the cleavage motif of PPEP-2, PLP↓PVP, is distinct from that of PPEP-1 (VNP↓PVP). As a result, an optimal substrate peptide for PPEP-2 was not cleaved by PPEP-1 and vice versa. To gain insight into the specificity mechanism of PPEP-2, we determined its crystal structure at 1.75 Å resolution and further confirmed the structure in solution using small-angle X-ray scattering (SAXS). We show that a four-amino-acid loop, which is distinct in PPEP-1 and -2 (GGST in PPEP-1 and SERV in PPEP-2), plays a crucial role in substrate specificity. A PPEP-2 variant, in which the four loop residues had been swapped for those from PPEP-1, displayed a shift in substrate specificity toward PPEP-1 substrates. Our results provide detailed insights into the PPEP-2 structure and the structural determinants of substrate specificity in this new family of PPEP proteases. PubMed: 29794027DOI: 10.1074/jbc.RA118.003244 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.75 Å) |
Structure validation
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