The Adaptable Binding Cleft of RmuAP1, a Pepsin-like Peptidase from <i>Rhodotorula mucilaginosa</i>, Enables the Enzyme to Degrade Immunogenic Peptides Derived from Gluten.

ABSTRACT: Celiac disease (CD) is an autoimmune disorder triggered by pepsin-resistant, gluten-derived immunogenic peptides (GIPs) in genetically predisposed individuals. Enzyme therapy targeting GIPs has been suggested as a complementary practice to a gluten-free diet to help reduce the symptoms of CD. Here, we present the crystal structure of RmuAP1, a pepsin-like aspartic protease from Rhodotorula mucilaginosa, which effectively degrades the toxic 33-mer and 26-mer GIPs under postprandial gastric conditions (pH 3.0-6.0). RmuAP1 has a canonical fold characteristic of the aspartic protease subfamily A1; however, it features a distinct flap and a flexible loop structure. Compared to pepsin, RmuAP1 accommodates the tetrapeptides PQQP and PQPQ, motifs frequently repeated on GIPs, via an adaptabl

SUBMITTER: Zhang YH 

PROVIDER: S-EPMC12730222 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature