6FPC

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

6FPC の概要

• エントリーDOI: 10.2210/pdb6fpc/pdb
• 分子名称: PRO-PRO endopeptidase, ZINC ION, CADMIUM ION, ... (5 entities in total)
• 機能のキーワード: endopeptidase, metalloprotease, zinc, hydrolase
• 由来する生物種: Paenibacillus alvei; 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 87775.53

構造登録者

Weeks, S.D.,Klychnikov, O.I.,Hensbergen, P.J.,Strelkov, S.V. (登録日: 2018-02-09, 公開日: 2018-05-30, 最終更新日: 2024-05-08)

主引用文献

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

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: 29794027
DOI: 10.1074/jbc.RA118.003244

実験手法

X-RAY DIFFRACTION (1.75 Å)