A5010536481- Protein Structure and Dynamics
- Enzyme Structure and Function
- Genomics and Phylogenetic Studies
- RNA and protein synthesis mechanisms
- Computational Drug Discovery Methods
- Machine Learning in Bioinformatics
- Bioinformatics and Genomic Networks
- HER2/EGFR in Cancer Research
- RNA Research and Splicing
- Microbial Metabolic Engineering and Bioproduction
- Hemoglobinopathies and Related Disorders
- Biochemical and Molecular Research
- Cardiac electrophysiology and arrhythmias
- Genetics, Bioinformatics, and Biomedical Research
- Polyamine Metabolism and Applications
- Enzyme Production and Characterization
- Heat shock proteins research
- RNA modifications and cancer
- Monoclonal and Polyclonal Antibodies Research
- Genomics and Rare Diseases
- Mass Spectrometry Techniques and Applications
- Photosynthetic Processes and Mechanisms
- Enzyme function and inhibition
- Metabolomics and Mass Spectrometry Studies
- PI3K/AKT/mTOR signaling in cancer
National University of Quilmes
2015-2024
Consejo Nacional de Investigaciones Científicas y Técnicas
2004-2023
University of Buenos Aires
2004
Fundación Instituto Leloir
2004
After the outstanding breakthrough of AlphaFold in predicting protein 3D models, new questions appeared and remain unanswered. The ensemble nature proteins, for example, challenges structural prediction methods because models should represent a set conformers instead single structures. evolutionary features captured by effective deep learning techniques may unveil information to generate several diverse conformations from sequence. Here we address performance AlphaFold2 predictions obtained...
Abstract The Protein Ensemble Database (PED) (https://proteinensemble.org), which holds structural ensembles of intrinsically disordered proteins (IDPs), has been significantly updated and upgraded since its last release in 2016. new version, PED 4.0, completely redesigned reimplemented with cutting-edge technology now about six times more data (162 versus 24 entries 242 60 ensembles) a broader representation state the art ensemble generation methods than previous version. database renewed...
CoDNaS (conformational diversity of the native state) is a protein conformational database. Conformational describes structural differences between conformers that define state proteins. It key concept to understand function and biological processes related functions. offers well curated database experimentally driven, thoroughly linked, annotated. facilitates extraction information on small based movements. enables users easily relate degree with physical, chemical properties derived from...
The RepeatsDB database (URL: https://repeatsdb.org/) provides annotations and classification for protein tandem repeat structures from the Protein Data Bank (PDB). repeats are ubiquitous in all branches of tree life. accumulation solved new possibilities detection, but also increasing need annotation. Here we present 3.0, which addresses these challenges presents an extended scheme. major conceptual change compared to previous version is hierarchical combining top levels based solely on...
Protein motions are a key feature to understand biological function. Recently, large-scale analysis of protein conformational diversity showed positively skewed distribution with peak at 0.5 Å C-alpha root-mean-square-deviation (RMSD). To this in terms structure-function relationships, we studied well curated and large dataset ~5,000 proteins experimentally determined diversity. We searched for global behaviour patterns studying how structure-based features change among the available...
Abstract Background Non-synonymous coding SNPs (nsSNPs) that are associated to disease can also be related with alterations in protein stability. Computational methods available predict the effect of single amino acid substitutions (SASs) on stability based a folded structure. However, native state is not unique and it better represented by ensemble its conformers dynamic equilibrium. The maintenance essential for function. In this work we investigated how conformational diversity affect...
Native state of proteins is better represented by an ensemble conformers in equilibrium than only one structure. The extension structural differences between characterizes the conformational diversity protein. In this study, we found a negative correlation and protein evolutionary rate. Conformational was expressed as maximum root mean square deviation (RMSD) available Diversity State database. Evolutionary rate estimations were calculated using 16 different species compared with human...
Glycogen and starch are the major energy storage compounds in most living organisms. The metabolic pathways leading to their synthesis involve action of several enzymes, among which glycogen synthase (GS) or (SS) catalyze elongation alpha-1,4-glucan backbone. At least five SS isoforms were described Arabidopsis thaliana; it has been reported that isoform III (SSIII) a regulatory function on transient plant starch. catalytic C-terminal domain A. thaliana SSIII (SSIII-CD) was cloned expressed....
It is well established that the conservation of protein structure during evolution constrains sequence divergence. The certain physicochemical environments to preserve folds and then biological function originates a site-specific structurally constrained substitution pattern. However, native not unique. known state better described by an ensemble conformers in dynamic equilibrium. In this work, we studied influence conformational diversity divergence evolution. For purpose, derived set 900...
Abstract Motivation: Conformational diversity is a key concept in the understanding of different issues related with protein function such as study catalytic processes enzymes, protein-protein recognition, evolution and origins new biological functions. Here, we present database proteins degrees conformational diversity. Diversity Native State (CoDNaS) redundant collection three-dimensional structures for same derived from data bank. Structures obtained under crystallographic conditions have...
Structural differences between conformers sustain protein biological function. Here, we studied in a large dataset of 745 intrinsically disordered proteins, how ordered-disordered transitions modulate structural as derived from crystallographic data. We found that almost 50% the proteins show no and have low conformational diversity while rest higher diversity. In this last subset, 60% become more ordered after ligand binding, 40% disordered. As is inherently connected with function our...
Abstract The starch‐synthase III (SSIII), with a total of 1025 residues, is one the enzymes involved in plants starch synthesis. SSIII from Arabidopsis thaliana contains putative N‐terminal transit peptide followed by 557‐amino acid SSIII‐specific domain (SSIII‐SD) three internal repeats and C‐terminal catalytic 450 amino acids. Here, using computational characterization techniques, we show that each encodes starch‐binding (SBD). Although A. its close homologous proteins no detectable...
Riboflavin, an essential cofactor for all organisms, is biosynthesized in plants, fungi and microorganisms. The penultimate step the pathway catalyzed by enzyme lumazine synthase. One of most distinctive characteristics this that it found different species two quaternary structures, pentameric icosahedral, built from practically same structural monomeric unit. In fact, icosahedral structure best described as a capsid twelve pentamers. Despite noticeable difference, active sites are virtually...
Epidermal Growth Factor Receptor (EGFR), a tyrosine kinase receptor, is one of the main tumor markers in different types cancers. The native state mainly composed two populations conformers: active and inactive. Several sequence variations EGFR region promote differential enrichment conformers with higher activity. Some structural characteristics have been proposed to differentiate conformations, but these considerations could lead ambiguous classifications. We present characterisation...
Tandem Repeat Proteins (TRPs) are a class of proteins with repetitive amino acid sequences that have been studied extensively for over two decades. Different features at the level sequence, structure, function and evolution attributed to them by various authors. And yet many its salient appear only when looking specific subclasses protein tandem repeats. Here, we attempt rationalize existing knowledge on pointing out several dichotomies. The emerging picture is more nuanced than generally...
Major scientific challenges that are beyond the capability of individuals need to be addressed by multi-disciplinary and multi-institutional consortia. Examples these endeavours include Human Genome Project, more recently, Structural Genomics (SG) initiative. The SG initiative pursues expansion structural coverage at least one representative for each protein family derive remaining structures using homology modelling. However, biological function is inherently connected with dynamics can...
Computational modeling of tertiary structures has become standard use to study proteins that lack experimental characterization. Unfortunately, 3D structure prediction methods and model quality assessment programs often overlook an ensemble conformers in equilibrium populates the native state proteins. In this work we collected sets publicly available protein models corresponding target experimentally solved studied how they describe conformational diversity protein. For each protein,...
Nqo15 is a subunit of respiratory complex I the bacterium Thermus thermophilus, with strong structural similarity to human frataxin (FXN), protein involved in mitochondrial disease Friedreich's ataxia (FRDA). Recently, we showed that expression recombinant can ameliorate phenotype FRDA patients' cells, and this prompted us further characterize both solution's behavior its potential functional overlap FXN, using combination silico vitro techniques. We studied analogy FXN by performing...
Massive parallel sequencing technologies are facilitating the faster identification of sequence variants with consequent capability untangling molecular bases many human genetic syndromes. However, it is not always easy to understand impact novel variants, especially for missense changes, which can lead a spectrum phenotypes. This study presents custom-designed multistep methodology evaluate aggregated in genome aggregation database HBB, HBA2, and HBA1 genes, by testing improving its...
Abstract After the outstanding breakthrough of AlphaFold in predicting protein 3D models, new questions appeared and remain unanswered. The ensemble nature proteins, for example, challenges structural prediction methods because models should represent a set conformers instead single structures. evolutionary features captured by effective deep learning techniques may unveil information to generate several diverse conformations from sequence. Here we address performance AlphaFold2 predictions...