A5090791470- Enzyme Structure and Function
- Computational Drug Discovery Methods
- Protein Structure and Dynamics
- Glycosylation and Glycoproteins Research
- Click Chemistry and Applications
- Amino Acid Enzymes and Metabolism
- Monoclonal and Polyclonal Antibodies Research
- Carbohydrate Chemistry and Synthesis
- Cell Image Analysis Techniques
- Biochemical and Molecular Research
- Algorithms and Data Compression
- melanin and skin pigmentation
- Chemical Synthesis and Analysis
- Educational Technology and Assessment
- Viral Infectious Diseases and Gene Expression in Insects
- Nanoplatforms for cancer theranostics
- Analytical Chemistry and Chromatography
- Neuroscience and Neuropharmacology Research
- Retinal Development and Disorders
- Photoreceptor and optogenetics research
- Alkaline Phosphatase Research Studies
- Complement system in diseases
- Data Mining Algorithms and Applications
- Iron Metabolism and Disorders
- Phosphodiesterase function and regulation
Åbo Akademi University
2000-2024
University of Turku
1996-2000
Turku Centre for Biotechnology
1996-2000
Soluble inorganic pyrophosphatase (PPase), an essential enzyme central to phosphorus metabolism, catalyzes the hydrolysis of phosphoanhydride bond in pyrophosphate. Catalysis requires divalent metal ions which affect apparent pKas general acid and base on enzyme, pKa substrate. Three five are required for maximal activity, depending pH source. A detailed understanding catalysis would aid both nature biological mechanisms phosphoryl transfer, role cations. Without a high-resolution complex...
Endosialidase (endo-N-acetylneuraminidase) is a tailspike enzyme of bacteriophages specific for human pathogenic Escherichia coli K1, which specifically recognizes and degrades polySia (polysialic acid). also polysaccharide the capsules other meningitis- sepsis-causing bacteria, post-translational modification NCAM (neural cell-adhesion molecule). We have cloned sequenced three spontaneously mutated endosialidases PK1A bacteriophage one PK1E display lost or residual activity but retain...
Reliable and effective virtual high-throughput screening (vHTS) methods are desperately needed to minimize the expenses involved in drug discovery projects. Here, we present an improvement negative image-based (NIB) screening: shape, electrostatics, solvation state of target protein's ligand-binding site included into vHTS. Additionally, initial vHTS results postprocessed with molecular mechanics/generalized Born surface area (MMGBSA) calculations estimate favorability ligand-protein...
Abstract In this study, we use an optogenetic inhibitor of c-Jun NH 2 -terminal kinase (JNK) in dendritic spine sub-compartments rat hippocampal neurons. We show that JNK inhibition exerts rapid (within seconds) reorganization actin the spine-head. Using real-time Förster resonance energy transfer (FRET) to measure activity, find either excitotoxic insult (NMDA) or endocrine stress (corticosterone), activate spine-head causing internalization AMPARs and retraction. Both events are prevented...
A detailed comparison of the structures aspartate aminotransferase, alanine race-mase, beta subunit tryptophan synthase, D-amino acid aminotransferase and glycogen phosphorylase has revealed more extensive structural similarities among pyridoxal phosphate (PLP)-binding domains in these enzymes than was observed previously. These consist seven common segments polypeptide chain, which form an organization backbone chain responsible for appropriate disposition key residues, some from aligned...
We have developed a generic tool for the automatic identification of regions local structural similarity in unrelated proteins having different folds, as well defining more global similarities that result from homologous protein structures. The computer program GENFIT has evolved genetic algorithm-based three-dimensional structure comparison GA_FIT.1, 2 GENFIT, however, can locate and superimpose homology regardless their position pair structures, fold topology, or chain direction....
The performance of molecular docking can be improved by comparing the shape similarity flexibly sampled poses against target proteins' inverted binding cavities. effectiveness these pseudo-ligands or negative image-based models in rescoring is boosted further performing enrichment-driven optimization. Here, we introduce a novel shape-focused pharmacophore modeling algorithm O-LAP that generates new class cavity-filling clumping together overlapping atomic content via pairwise distance graph...
Abstract Three ATP‐dependent enzymes with different folds, cAMP‐dependent protein kinase, D‐Ala:D‐Ala ligase and the α‐subunit of α 2 β ribonucleotide reductase, have a similar organization their ATP‐binding sites. The most meaningful similarity was found over 23 structurally equivalent residues in each includes three strands from β‐sheets, addition to connecting loop. secondary structure elements these donate four amino acids forming key hydrogen bonds responsible for common orientation...
Abstract Two proteins, D‐alanine:D‐alanine ligase and cAMP‐dependent protein kinase, share a remarkable degree of structural convergence despite having different three‐dimensional folds enzymatic functions. Here we report that as many 103 residues from 10 segments form two identical super‐secondary structures between which the cofactor ATP is bound. The cofactor, bound metal cations, several water molecules large network electrostatic hydrophobic interactions common to both enzymes, these...
Molecular docking is a key method used in virtual screening (VS) campaigns to identify small-molecule ligands for drug discovery targets. While provides tangible way understand and predict the protein-ligand complex formation, algorithms are often unable separate active from inactive molecules practical VS usage. Here, novel shape-focused pharmacophore protocol demonstrated facilitating effective hit using retinoic acid receptor-related orphan receptor gamma t (RORγt) as case study. RORγt...
We introduce a statistical method for evaluating atomic level 3D interaction patterns of protein-ligand contacts. Such can be used fast separation likely ligand and binding site combinations out all those that are geometrically possible. The practical purpose this probabilistic is molecular docking scoring, as an essential part scoring function. Probabilities calculated conditional on structural x-ray data predefined chemical classification fragment types. Spatial coordinates atoms modeled...
Molecular docking is a key in silico method used routinely modern drug discovery projects. Although provides high-quality ligand binding predictions, it regularly fails to separate the active compounds from inactive ones. In negative image-based rescoring (R-NiB), shape/electrostatic potential (ESP) of poses compared image protein's cavity. While R-NiB often improves yield considerably, cavity-based models do not reach their full without expert editing. Accordingly, greedy search-driven...
Despite the pivotal role of molecular docking in modern drug discovery, default scoring functions often fail to recognize active ligands virtual screening campaigns. Negative image-based rescoring improves enrichment by comparing shape/electrostatic potential (ESP) flexible poses against target protein’s inverted cavity volume. By optimizing these negative (NIB) models using a greedy search, yield can be improved massively and consistently. Here, fundamental modification is implemented this...