Identification of NAD interacting residues in proteins

Background  

Small molecular cofactors or ligands play a crucial role in the proper functioning of cells. Accurate annotation of their target proteins and binding sites is required for the complete understanding of reaction mechanisms. Nicotinamide adenine dinucleotide (NAD⁺ or NAD) is one of the most commonly used organic cofactors in living cells, which plays a critical role in cellular metabolism, storage and regulatory processes. In the past, several NAD binding proteins (NADBP) have been reported in the literature, which are responsible for a wide-range of activities in the cell. Attempts have been made to derive a rule for the binding of NAD⁺ to its target proteins. However, so far an efficient model could not be derived due to the time consuming process of structure determination, and limitations of similarity based approaches. Thus a sequence and non-similarity based method is needed to characterize the NAD binding sites to help in the annotation. In this study attempts have been made to predict NAD binding proteins and their interacting residues (NIRs) from amino acid sequence using bioinformatics tools.     

HOX cofactors expression and regulation in the human ovary

Background  

HOX cofactors enhance HOX binding affinities and specificities and increase HOX's unique functional activities. The expression and the regulation of HOX cofactors in human ovaries are unknown.     

Pleiotropic effects of the twin-arginine translocation system on biofilm formation, colonization, and virulence in Vibrio cholerae

Background  

The Twin-arginine translocation (Tat) system serves to translocate folded proteins, including periplasmic enzymes that bind redox cofactors in bacteria. The Tat system is also a determinant of virulence in some pathogenic bacteria, related to pleiotropic effects including growth, motility, and the secretion of some virulent factors. The contribution of the Tat pathway to Vibrio cholerae has not been explored. Here we investigated the functionality of the Tat system in V. cholerae, the etiologic agent of cholera.     

Prediction of transmembrane helix orientation in polytopic membrane proteins

Background  

Membrane proteins compose up to 30% of coding sequences within genomes. However, their structure determination is lagging behind compared with soluble proteins due to the experimental difficulties. Therefore, it is important to develop reliable computational methods to predict structures of membrane proteins.     

Classification of protein quaternary structure by functional domain composition

Background  

The number and the arrangement of subunits that form a protein are referred to as quaternary structure. Quaternary structure is an important protein attribute that is closely related to its function. Proteins with quaternary structure are called oligomeric proteins. Oligomeric proteins are involved in various biological processes, such as metabolism, signal transduction, and chromosome replication. Thus, it is highly desirable to develop some computational methods to automatically classify the quaternary structure of proteins from their sequences.     

Synthesizing non-natural parts from natural genomic template

Background  

The current knowledge of genes and proteins comes from 'naturally designed' coding and non-coding regions. It would be interesting to move beyond natural boundaries and make user-defined parts. To explore this possibility we made six non-natural proteins in E. coli. We also studied their potential tertiary structure and phenotypic outcomes.     

Reduced-folate carrier (RFC) is expressed in placenta and yolk sac,as well as in cells of the developing forebrain,hindbrain, neural tube,craniofacial region,eye, limb buds and heart

Background  

Folate is essential for cellular proliferation and tissue regeneration. As mammalian cells cannot synthesize folates de novo, tightly regulated cellular uptake processes have evolved to sustain sufficient levels of intracellular tetrahydrofolate cofactors to support biosynthesis of purines, pyrimidines, and some amino acids (serine, methionine). Though reduced-folate carrier (RFC) is one of the major proteins mediating folate transport, knowledge of the developmental expression of RFC is lacking. We utilized in situ hybridization and immunolocalization to determine the developmental distribution of RFC message and protein, respectively.     

Detecting internally symmetric protein structures

Background  

Many functional proteins have a symmetric structure. Most of these are multimeric complexes, which are made of non-symmetric monomers arranged in a symmetric manner. However, there are also a large number of proteins that have a symmetric structure in the monomeric state. These internally symmetric proteins are interesting objects from the point of view of their folding, function, and evolution. Most algorithms that detect the internally symmetric proteins depend on finding repeating units of similar structure and do not use the symmetry information.     

Phosphatase inhibitor 2 promotes acetylation of tubulin in the primary cilium of human retinal epithelial cells

Background  

Primary cilia are flagella-like projections from the centriole of mammalian cells that have a key role in cell signaling. Human diseases are linked to defects in primary cilia. Microtubules make up the axoneme of cilia and are selectively acetylated and this is thought to contribute to the stability of the structure. However, mechanisms to regulate tubulin acetylation in cilia are poorly understood.     

The LabelHash algorithm for substructure matching

Background  

There is an increasing number of proteins with known structure but unknown function. Determining their function would have a significant impact on understanding diseases and designing new therapeutics. However, experimental protein function determination is expensive and very time-consuming. Computational methods can facilitate function determination by identifying proteins that have high structural and chemical similarity.     

Characterization of the interaction between Actinin-Associated LIM Protein (ALP) and the rod domain of α-actinin

Background  

The PDZ-LIM proteins are a family of signalling adaptors that interact with the actin cross-linking protein, α-actinin, via their PDZ domains or via internal regions between the PDZ and LIM domains. Three of the PDZ-LIM proteins have a conserved 26-residue ZM motif in the internal region, but the structure of the internal region is unknown.     

Evolutionary history of histone demethylase families: distinct evolutionary patterns suggest functional divergence

Background  

Histone methylation can dramatically affect chromatin structure and gene expression and was considered irreversible until recent discoveries of two families of histone demethylases, the KDM1 (previously LSD1) and JmjC domain-containing proteins. These two types of proteins have different functional domains and distinct substrate specificities. Although more and more KDM1 and JmjC proteins have been shown to have histone demethylase activity, our knowledge about their evolution history is limited.     

K2D2: Estimation of protein secondary structure from circular dichroism spectra

Background  

Circular dichroism spectroscopy is a widely used technique to analyze the secondary structure of proteins in solution. Predictive methods use the circular dichroism spectra from proteins of known tertiary structure to assess the secondary structure contents of a protein with unknown structure given its circular dichroism spectrum.     

Structural genomics of human proteins – target selection and generation of a public catalogue of expression clones

Background  

The availability of suitable recombinant protein is still a major bottleneck in protein structure analysis. The Protein Structure Factory, part of the international structural genomics initiative, targets human proteins for structure determination. It has implemented high throughput procedures for all steps from cloning to structure calculation. This article describes the selection of human target proteins for structure analysis, our high throughput cloning strategy, and the expression of human proteins in Escherichia colihost cells.     

Protein structure similarity from principle component correlation analysis

Background  

Owing to rapid expansion of protein structure databases in recent years, methods of structure comparison are becoming increasingly effective and important in revealing novel information on functional properties of proteins and their roles in the grand scheme of evolutionary biology. Currently, the structural similarity between two proteins is measured by the root-mean-square-deviation (RMSD) in their best-superimposed atomic coordinates. RMSD is the golden rule of measuring structural similarity when the structures are nearly identical; it, however, fails to detect the higher order topological similarities in proteins evolved into different shapes. We propose new algorithms for extracting geometrical invariants of proteins that can be effectively used to identify homologous protein structures or topologies in order to quantify both close and remote structural similarities.     

An evolutionary method for learning HMM structure: prediction of protein secondary structure

Background  

The prediction of the secondary structure of proteins is one of the most studied problems in bioinformatics. Despite their success in many problems of biological sequence analysis, Hidden Markov Models (HMMs) have not been used much for this problem, as the complexity of the task makes manual design of HMMs difficult. Therefore, we have developed a method for evolving the structure of HMMs automatically, using Genetic Algorithms (GAs).     

Protein structure search and local structure characterization

Background  

Structural similarities among proteins can provide valuable insight into their functional mechanisms and relationships. As the number of available three-dimensional (3D) protein structures increases, a greater variety of studies can be conducted with increasing efficiency, among which is the design of protein structural alphabets. Structural alphabets allow us to characterize local structures of proteins and describe the global folding structure of a protein using a one-dimensional (1D) sequence. Thus, 1D sequences can be used to identify structural similarities among proteins using standard sequence alignment tools such as BLAST or FASTA.