6fpc

Structure of the PRO-PRO endopeptidase (PPEP-2) from Paenibacillus alvei

spinqualitylabelsall models 6fpc, resolution 1.75Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6fpc is a 4 chain structure with sequence from Paenibacillus alvei. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.75Å Ligands: CD, SO4, ZN Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function PPEP2_PAEA2 Zinc-dependent endoprotease with a unique preference for proline residues surrounding the scissile bond, which cleaves in a PLP-|-PVP motif. Cleaves the cell surface protein encoded by an adjacent gene, which contains two PPEP-2 cleaving sites and putative extracellular matrix-binding domains. Thereby, may have a role in the regulation of P.alvei adhesion. Is not able to cleave within the PVP-|-PVQ motif, and only shows a very poor cleavage of the VNP-|-PVP motif in vitro, which is the optimal substrate peptide for PPEP-1 from P.difficile. Publication Abstract from PubMed 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 Clostridium difficile (PPEP-1) cleaves two C. difficile cell-surface proteins involved in adhesion, one of which is encoded by the gene adjacent to the ppep-1 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 Paenibacillus alvei, 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 A 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. Discovery of a new Pro-Pro endopeptidase, PPEP-2, provides mechanistic insights into the differences in substrate specificity within the PPEP family.,Klychnikov OI, Shamorkina TM, Weeks SD, van Leeuwen HC, Corver J, Drijfhout JW, van Veelen PA, Sluchanko NN, Strelkov SV, Hensbergen PJ J Biol Chem. 2018 May 23. pii: RA118.003244. doi: 10.1074/jbc.RA118.003244. PMID:29794027 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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