[Analysis of Multiple Protein Alignments Using 3D-Structural Information on the Orientation of Amino Acid Side-Chains].

Multiple alignment of amino acid sequences of homologous proteins is a key tool in state-of-the-art bioinformatics and evolutionary analysis. Differences in the spatial orientation of amino acid side-chains can predetermine significant functional diversity among members of one superfamily; however, this is usually not taken into account in any way when constructing alignments and during subsequent comparative analysis. First of all, this is due to the limitation of existing algorithms, which are guided by the biochemical similarity of the "alphabet" of amino acid substitutions and either do not use information about the 3D-structural organization of proteins at all, or are limited to comparing the backbone only (i.

Loop 422-437 in NanA from Streptococcus pneumoniae plays the role of an active site lid and is associated with allosteric regulation.

Neuraminidase A from Streptococcus pneumoniae (NanA) is considered a potentially key pathogenicity factor and a promising drug target to treat human infectious diseases. Computational and experimental efforts are increasingly being used to study its structure and function which yet remain poorly understood. In this work, we characterized structural dynamics of NanA's active site and gained novel mechanistic insights into its implications for a ligand binding.

Guide tree optimization with genetic algorithm to improve multiple protein 3D-structure alignment.

Motivation: With the increasing availability of 3D-data, the focus of comparative bioinformatic analysis is shifting from protein sequence alignments toward more content-rich 3D-alignments. This raises the need for new ways to improve the accuracy of 3D-superimposition.

Results: We proposed guide tree optimization with genetic algorithm (GA) as a universal tool to improve the alignment quality of multiple protein 3D-structures systematically.

Probing the role of the residues in the active site of the transaminase from Thermobaculum terrenum.

Creating biocatalysts for (R)-selective amination effectively is highly desirable in organic synthesis. Despite noticeable progress in the engineering of (R)-amine activity in pyridoxal-5'-phosphate-dependent transaminases of fold type IV, the specialization of the activity is still an intuitive task, as there is poor understanding of sequence-structure-function relationships. In this study, we analyzed this relationship in transaminase from Thermobaculum terrenum, distinguished by expanded substrate specificity and activity in reactions with L-amino acids and (R)-(+)-1-phenylethylamine using α-ketoglutarate and pyruvate as amino acceptors.

Bioinformatic Analysis of the Nicotinamide Binding Site in Poly(ADP-Ribose) Polymerase Family Proteins.

The PARP family consists of 17 members with diverse functions, including those related to cancer cells' viability. Several PARP inhibitors are of great interest as innovative anticancer drugs, but they have low selectivity towards distinct PARP family members and exert serious adverse effects. We describe a family-wide study of the nicotinamide (NA) binding site, an important functional region in the PARP structure, using comparative bioinformatic analysis and molecular modeling.