Biomineralizing organisms use organic molecules to generate species-specific mineral patterns. Here, we describe the chemical structure of long-chain polyamines (up to 20 repeated units), which represent the main organic constituent of diatom biosilica. These substances are the longest polyamine chains found in nature and induce rapid silica precipitation from a silicic acid solution. Each diatom is equipped with a species-specific set of polyamines and silica-precipitating proteins, which are termed silaffins. Different morphologies of precipitating silica can be generated by polyamines of different chain lengths as well as by a synergistic action of long-chain polyamines and silaffins.T he biological formation of inorganic structures, termed biominerals, is a widespread phenomenon in nature (1). Among the most famous examples are unicellular algaediatoms-that possess a cell wall composed of silica and organic molecules or macromolecules (2). Most interestingly, diatom biosilica displays a dazzling variety of species-specific silica patterns that are structured on a nanometer-to-micrometer scale (3-6). Elucidating the mechanism that controls production of nanostructured biosilica is a fascinating biochemical problem and, in addition, is of great interest in materials chemistry. Biomimetic approaches are believed to allow the production of advanced materials at ambient temperature and with high precision, which are expected to exhibit superior properties in a wide range of applications (7,8). Reaching this goal, however, requires a detailed knowledge of the organic molecules that govern silica biomineralization.Recently, cationic polypeptides (called silaffins) isolated from purified cell walls of the diatom Cylindrotheca fusiformis were shown to generate networks of silica nanospheres within seconds when added to a solution of silicic acid (9). The silaffins are tightly associated with the biosilica so that they can only be solubilized after dissolution of the cell wall in hydrogen fluoride (HF). Silaffin-1 contains a previously undescribed type of protein modification, a polyamine consisting of 6-11 repeats of the N-methyl-propylamine unit (a mass increment of 71 Da per repeat) covalently attached to specific lysine residues (9). It is probably this structural element that accelerates silicic acid polymerization and promotes production of nanosphere networks. Previously, ultrastructural work on cell wall biogenesis in a number of diatoms led to the conclusion that silica appears to be deposited in different forms during valve morphogenesis. Especially evident was the participation of silica spheres ranging up to 100 nm in diameter (4, 10). If silaffins are indeed involved in the process of pattern formation that creates the amazingly rich variety of diatom shell silica structures, then different diatom species are expected to contain different types of silaffins or silaffin-like molecules. We therefore analyzed the HFextractable organic cell wall components from a wide range of diatom species. Surprisingly, th...

Diatoms possess silica‐based cell walls with species‐specific structures and ornamentations. Silica deposition in diatoms offers a model to study the processes involved in biomineralization. A new wall is produced in a specialized vesicle (silica deposition vesicle, SDV) and secreted. Thus proteins involved in wall biogenesis may remain associated with the mature cell wall. Here it is demonstrated that EDTA treatment removes most of the proteins present in mature cell walls of the marine diatom Cylindrotheca fusiformis. A main fraction consists of four related glycoproteins with a molecular mass of approximately 75 kDa. These glycoproteins were purified to homogeneity. They consist of repeats of Ca2+ binding domains separated by polypeptide stretches containing hydroxyproline. The proteins in the EDTA extract aggregate and precipitate in the presence of Ca2+. Immunological studies detected related proteins in the cell wall of the freshwater diatom Navicula pelliculosa, indicating that these proteins represent a new family of proteins that are involved in the biogenesis of diatom cell walls.

The outstanding feature of a diatom is the species-specific design and ornamentation of the silicabased cell wall, termed frustulum. A new frustulum is shaped in a specialized organelle (silica deposition vesicle) and secreted. Proteins in the lumen of this organelle may control the biomineralization process and are likely to remain associated with the mature cell wall. Therefore a study of the structures of proteins associated with the diatom cell wall was initiated. The complete primary structures of three cell wall proteins (denoted as frustulins) have been determined. In addition, partial amino acid sequences from two more cell wall components were obtained. From these data, a highly conserved domain has been identified as a common building block of diatom cell wall proteins that is repeated several time; per polypeptide chain together with polyproline/hydroxyproline or polyglycine spacers. All frustulins characterized so far, are synthesized as preproteins with a novel type of N-terminal presequence.Keywords: diatom ; cell wall; hydroxyproline-rich glycoprotein ; presequence; Cylindrotheca fusiformis.The cell wall of diatoms is composed of amorphous, hydrated silica and organic components (Volcani, 1981). The species-specific design and ornamentation of the cell wall's silica skeleton is the most fascinating aspect of diatom biology and the basis for diatom systematics. It was estimated that there are more than 10 000 recent diatom species each displaying a different cell wall structure (Pickett-Heaps et al., 1990). The diatom cell wall (also termed frustulum or frustle) consists of two parts, the epitheca and the hypotheca. Each theca is composed of a valve and several silica strips (girdle bands). It is the girdle band region in which epitheca and hypotheca overlap (see Fig. 1).New valves are produced after cell division and cytokinesis of the mother protoplast. The resulting daughter protoplasts are trapped within the mother cell wall. Each daughter protoplast produces a new valve in a specialized intracellular organelle, the silica deposition vesicle (Volcani, 1981). In this organelle the polymerization of silicate takes place. The vesicle develops closely beneath the plasma membrane and extends during the process of silica deposition. Finally, it spans the whole area beneath the plasma membrane, containing a new valve. The latter is exocytosed and the daughter cells separate, each possessing a maternal epitheca and a newly formed hypotheca. It is suggested that cytoskeleton and cytoplasmic organells take part in shaping the silica deposition vesicle and thus are determinants of cell wall morphology . In addition it is assumed that an organic matrix within the vesicle may exert influence on the fine patterning of the cell wall (Pickett-Heaps et al., 1990). This is an attractive hypothesis, since certain organic macromolecules are known to function as templates and regulators for inorganic crystal growth in vitro (Weiner and Addadi, 1991).The species-specific structure of a diatom cell wall demands genet...

The hydrogen bond occurred between the Tetrakis (4-aminopyridine-kN1) di chloride copper (II) monohydrate and Human Serine Racemase and Sphingosine 1-phosphate (S1P) lyase identified using molecular docking tool (Auto dock tools) to understand the drug-drug interaction. Based on the crystallographic structure of Tetrakis (4-aminopyridine-kN1) di chloride copper (II) monohydrate with enzyme and protein obtained using Auto dock tools and analysis through hirshfeld surface show that the Hydrogen bonding interaction is restricted by N-H…O hydrogen bonding and both the molecular structure show the hydrophilic interactions. Docked structure of S1P and HSR with ligand closely contact protein interactions of N....H....O and N-H...0 hydrogen bonding shows on the complex function of hirshiefield surface in molecular goemetry. It shapes relies on the interactions between Macromelecule of protein-ligand as well as atoms using crystal explorer The human serine racemase and the ligand interact through N(4-aminopyridine)-H…O(Serine) and N(4-aminopyridine)-H…O(Asparagine) hydrogen bonding with bond distance 2.05Å and 2.07Å respectively and the estimated Free Energy of Binding is-5.81 kcal/mol and estimated Inhibition Constant, Ki is 54.66 μM (micro molar) [Temperature = 298.15 K].The Sphingosine 1-phosphate (S1P) lyase and the ligand interact through N(4-aminopyridine)-H…O(Glutamine) and N(4-aminopyridine)-H… O(Valine) hydrogen bonding with bond distance 1.97Å and 1.91Å respectively and the estimated Free Energy of Binding is-5.32 kcal/mol and estimated Inhibition Constant, Ki is 126.74μM (micromolar) [Temperature = 298.15 K].The antibiotic sensitivity study of Tetrakis (4-aminopyridine-kN1) di chloride copper (II) monohydrate with the microorganisms like Escherichia coli and Streptomyces show that it has less antibiotic sensitivity with these microorganisms. These studies identify the possibilities of Tetrakis (4-aminopyridine-kN1) di chloride copper (II) monohydrate to act as drug with required changes in its molecular structure. These analysis are recently application of inhibitory action of therapeutic target for treatment of Multiple Sceloris(MS). 4-Aminopyridine metal complex increase neurological effects in pottasium(K+) channel blockade. In the field of antineoplastic drug development the transition metals are dynamic in electron affinity, reactivity and geometry. For the drug chemist the usage of transition metals act as a effective tool to develop and study molecules-drug interactions. [1] Tetrakis(4-aminopyridine-κN1) dichloridocopper(II)monohydrate,ActaCryst (2008) E64, page m853-m854 [2] J. K. Zaręba, M. J. Białek, J. Janczak, J. Zon, A. Dobosz, Cryst Growth Des 14 (2014) 6143-6153. [3] Weiler S, Braendlin N, Beerli C, Bergsdorf C, Schubart A, Srinivas H, Oberhauser B, Billich A.,Orally active 7-substituted (4-benzylphthalazin-1-yl)-2-methylpiperazin1yl]nicotinonitriles as active-site inhibitors of sphingosine 1-phosphate lyase for the treatment of multiple sclerosis.

CLK2 inhibition has been proposed as a potential mechanism to improve autism and neuronal functions in Phelan-McDermid syndrome (PMDS). Herein, the discovery of a very potent indazole CLK inhibitor series and the CLK2 X-ray structure of the most potent analogue are reported. This new indazole series was identified through a biochemical CLK2 Caliper assay screen with 30k compounds selected by an in silico approach. Novel high-resolution X-ray structures of all CLKs, including the first CLK4 X-ray structure, bound to known CLK2 inhibitor tool compounds (e.g., TG003, CX-4945), are also shown and yield insight into inhibitor selectivity in the CLK family. The efficacy of the new CLK2 inhibitors from the indazole series was demonstrated in the mouse brain slice assay, and potential safety concerns were investigated. Genotoxicity findings in the human lymphocyte micronucleus test (MNT) assay are shown by using two structurally different CLK inhibitors to reveal a major concern for pan-CLK inhibition in PMDS.