@article {149369, title = {Computational analysis of human gut microbial prolyl oligopeptidases (POPs) reveal candidate genes as therapeutics for celiac disease.}, journal = {Sci Rep}, volume = {14}, year = {2024}, month = {2024 Aug 23}, pages = {19641}, abstract = {

Celiac disease (CD) is a common autoimmune disorder in which the patients are unable to digest gluten, which is present in foods made up of wheat, barley and rye. Whilst diagnosis happens late in 80\% of the cases, avoidance of such foods appears to be the common solution. Alternative management strategies are required for the patients and their families since CD is also genetically carried over. Probiotic therapeutics and the consumption of appropriate enzymes, such as prolyloligopeptidases (POPs), from gut-friendly bacteria could reduce the disease burden and provide a better lifestyle for CD patients. We have examined around 5000 gut bacterial genomes and identified nearly 4000 non-redundant putative POPs. A select set of 10 gut bacterial POP sequences were subject to three-dimensional modelling, ligand docking and molecular dynamics simulations where stable interactions were observed between the POPs and gluten peptides. Our study provides sequence and structural analysis of potential POP enzymes in gut bacterial genomes, which form a strong basis to offer probiotic solutions to CD patients. In particular, these enzymes could be lead future therapeutics for this disease.

}, keywords = {Bacteria, Celiac Disease, Computational Biology, Gastrointestinal Microbiome, Glutens, Humans, Molecular Docking Simulation, Molecular Dynamics Simulation, Probiotics, Prolyl Oligopeptidases, Serine Endopeptidases}, issn = {2045-2322}, doi = {10.1038/s41598-024-70079-1}, author = {Nayak, Soumya and Regati, Dheemanth Reddy and Sowdhamini, Ramanathan} } @article {109312, title = {PASS2.7: a database containing structure-based sequence alignments and associated features of protein domain superfamilies from SCOPe.}, journal = {Database (Oxford)}, volume = {2022}, year = {2022}, month = {2022 Apr 12}, abstract = {

Sequence alignments are models that capture the structural, functional and evolutionary relationships between proteins. Structure-guided sequence alignments are helpful in the case of distantly related proteins with poor sequence identity, thus rendering routine sequence alignment methods ineffective. Protein Alignment organized as Structural Superfamilies or PASS2 database provides such sequence alignments of protein domains within a superfamily as per the Structural Classification of Proteins extended (SCOPe) database. The current update of PASS2 (i.e. PASS2.7) is following the latest release of SCOPe (2.07) and we provide data for 14 323 protein domains that are \<40\% identical and are organized into 2024 superfamilies. Several useful features derived from the alignments, such as conserved secondary structural motifs, HMMs and residues conserved across the superfamily, are also reported. Protein domains that are deviant from the rest of the members of a superfamily may compromise the quality of the alignment, and we found this to be the case in \~{}7\% of the total superfamilies we considered. To improve the alignment by objectively identifying such {\textquoteright}outliers{\textquoteright}, in this update, we have used a k-means-based unsupervised machine learning method for clustering superfamily members, where features provided were length of domains aligned, Cα-RMSD derived from the rigid-body superposition of all members and gaps contributed to the alignment by each domain. In a few cases, we have split the superfamily as per the clusters predicted and provided complete data for each cluster. A new feature included in this update is absolutely conserved interactions (ACIs) between residue backbones and side chains, which are obtained by aligning protein structure networks using structure-guided sequence alignments of superfamilies. ACIs provide valuable information about functionally important residues and the structure-function relationships of proteins. The ACIs and the corresponding conserved networks for backbone and sidechain have been marked on the superimposed structure separately.

DATABASE URL: The updated version of the PASS2 database is available at http://caps.ncbs.res.in/pass2/.

}, keywords = {Databases, Protein, Protein Domains, Protein Structure, Tertiary, Proteins, Sequence Alignment}, issn = {1758-0463}, doi = {10.1093/database/baac025}, author = {Bhattacharyya, Teerna and Nayak, Soumya and Goswami, Smit and Gadiyaram, Vasundhara and Mathew, Oommen K and Sowdhamini, Ramanathan} }