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Background: Titin is a gigantic protein located in the thick filament of vertebrate muscles. The putative functions of titin range from interactions with myosin and other muscle proteins to a role in muscle recoil. Analysis of its complete sequence has shown that titin is a multi-domain protein containing several copies of modules of 100 amino acids each. These are thought to belong to the fibronectin...
Background: Insect defensin A is a basic 4 kDa protein secreted by Phormia terranovae larvae in response to bacterial challenges or injuries. Previous biological tests suggest that the bacterial cytoplasmic membrane is the target of defensin A. The structural study of this protein is the first step towards establishing a structure–activity relationship and forms the basis for understanding its antibiotic...
Background: The polypeptide anthopleurin-B (AP-B) is one of a number of related toxins produced by sea anemones. AP-B delays inactivation of the voltage-gated sodium channel of excitable tissue. In the mammalian heart, this effect is manifest as an increase in the force of contraction. As a result, there is interest in exploiting the anthopleurins as lead compounds in the design of novel cardiac stimulants...
Background: The thrombolytic serine protease tissue-type plasminogen activator (t-PA) is a classical modular protein consisting of three types of domain in addition to the serine protease domain: F1 (homologous to fibronectin type I); G (epidermal growth factor-like) and kringle. Biochemical data suggest that the F1 and G modules play a major role in the binding of t-PA to fibrin and to receptors...
Background: The Mu Ner protein is a small (74 amino acids), basic, DNA-binding protein found in phage Mu. It belongs to a class of proteins, the cro and repressor proteins, that regulate the switch from the lysogenic to the lytic state of the phage life cycle. There is no significant sequence identity between Mu Ner and the cro proteins of other phages, despite their functional similarity. In addition,...
Background: The purine repressor (PurR) regulates genes that encode enzymes for purine biosynthesis. PurR has a two domain structure with an N-terminal DNA-binding domain (DBD) and a C-terminal corepressor-binding domain (CBD). The three-dimensional structure of a ternary complex of PurR bound to both corepressor and a specific DNA sequence has recently been determined by X-ray crystallography.Results...
Background: The pleckstrin homology (PH) domain, which is approximately 100 amino acids long, has been found in about 70 proteins involved in signal transduction and cytoskeletal function, a frequency comparable to SH2 (src homology 2) and SH3 domains. PH domains have been shown to bind the βγ-subunits of G-proteins and phosphatidylinositol 4,5-bisphosphate (PIP 2 ). It is conceivable that...
Background: The Kunitz-type inhibitor motif is found at the C terminus of the human collagen α3(VI) chain. This 76-residue module (domain C5) was prepared in recombinant form and showed high stability against proteases; however, it lacked any inhibitory activity against trypsin, thrombin, kallikrein and several other proteases. We have undertaken the determination of the three-dimensional (3D) structure...
Background: The giant muscle protein titin forms a filament which spans half of the sarcomere and performs, along its length, quite diverse functions. The region of titin located in the sarcomere I-band is believed to play a major role in extensibility and passive elasticity of muscle. In the I-band, the titin sequence consists mostly of repetitive motifs of tandem immunoglobulin-like (Ig) modules...
Background: Triplex formation is an approach of potential use in regulating and mapping of gene sequences. However, such applications have been limited to homogeneous sequences consisting of stretches of purines or pyrimidines. Understanding how heterogeneous duplexes are recognized by a third strand oligonucleotide at the atomic resolution level is an essential step toward broadening the application...
Background: Human thioredoxin (hTRX) is a 12 kDa cellular redox protein that has been shown to play an important role in the activation of a number of transcriptional and translational regulators via a thiol-redox mechanism. This activity may be direct or indirect via another redox protein known as Ref-1. The structure of a complex of hTRX with a peptide comprising its target from the transcription...
Background: RNA splicing is both ubiquitous and essential for the maturation of precursor mRNA molecules in eukaryotes. The process of trans-splicing involves the transfer of a short spliced leader (SL) RNA sequence to a consensus acceptor site on a separate pre-mRNA transcript. In Caenorhabditis elegans, a majority of pre-mRNA transcripts receive the 22-nucleotide SL from the SL1 RNA. Very little...
Background: The Src family of tyrosine kinases is involved in the propagation of intracellular signals from many transmembrane receptors. Each member of the family contains two domains that regulate interactions with other molecules, one of which is the Src homology 3 (SH3) domain. Although structures have previously been determined for SH3 domains, and ideas about peptide-binding modes have been...
Background S100B (S100β) is a member of the S100 family of small calcium-binding proteins: members of this family contain two helix-loop-helix calcium-binding motifs and interact with a wide range of proteins involved mainly in the cytoskeleton and cell proliferation. S100B is a neurite-extension factor and levels of S100B are elevated in the brains of patients with Alzheimer's disease or Down's syndrome:...
Background: Gene 3 protein (g3p), a minor coat protein from bacteriophage fd mediates infection of Escherichia coli bearing an F-pilus. Its N-terminal domain (g3p-D1) is essential for infection and mediates penetration of the phage into the host cytoplasm presumbly through interaction with the Tol complex in the E. coli membranes. Structural knowledge of g3p-D1 is both important for a molecular understanding...
Background: Fibronectin is an extracellular matrix glycoprotein involved in cell adhesion and migration events in a range of important physiological processes. Aberrant adhesion of cells to the matrix may contribute to the breakdown of normal tissue function associated with various diseases. The adhesive properties of fibronectin may be mediated by its interaction with collagen, the most abundant...
Background: Research on high-alkaline proteases, such as serine protease PB92, has been largely inspired by their industrial application as protein-degrading components of washing powders. Serine protease PB92 is a member of the subtilase family of enzymes, which has been extensively studied. These studies have included exhaustive protein engineering investigations and X-ray crystallography, in order...
Background: Solvated metal ions are critical for the proper folding and function of RNA. Despite the importance of these ions, the details of specific metal ion-RNA interactions are poorly understood. The crystal structure of a group I intron ribozyme domain characterized several metal-binding sites in the RNA with osmium (III) hexammine bound in the major groove. A corresponding method for locating...
Background: Carbohydrate-binding domains are usually small and physically separate from the catalytic domains of hydrolytic enzymes. Glucoamylase 1 (G1) from Aspergillus niger, an enzyme used widely in the food and brewing industries, contains a granular starch binding domain (SBD) which is separated from the catalytic domain by a semi-rigid linker. The aim of this study was to determine how the SBD...
Background: Eukaryotic genes are usually transcribed as precursor mRNAs which are then spliced, removing introns to produce functional mRNAs. Splicing is performed by the spliceosome and provides an important level of post-translational control of gene expression. Stem loop IIa from U2 small nuclear (sn)RNA is required for the efficient association of the U2 small nuclear ribonuclear protein (snRNP)...
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